Kinases - Tocris Bioscience · Protein Kinases aGC Group ... 2546 PKI 14-22 amide, myristoylated Cell-permeable PKA inhibitor 1 mg PKC (Protein Kinase C) Activators 2383 Bryostatin

Kinases

Kinase products by Group:• AGC Group• CAMK Group• CK1 Group• CMGC Group• STE Group• TK Group• TKL Group

Russell LupinLupinus polyphyllusA source of Genistein

Product Listing | Edition 3

Tocris Product Listing Series

2 |

Protein Kinases

aGC Group.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4Akt/PKB.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4MSK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4PDK1.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4PKA.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4PKC.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4PKG.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5ROCK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6RSK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6SGK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6

CaMK Group.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7AMPK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7CaMK.II... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7Chk.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7DAPK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8MK2.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8MLCK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8MnK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8NUAK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8Pim.Kinase.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8PKD.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8SIK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8STK33.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

CK1 Group.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9CK1.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

CMGC Group.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Cdk.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10CK2.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Clk.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10DYRK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10ERK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11GSK-3.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11JNK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12p38.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13SRPK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

ste Group.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14ASK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14MEK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14PAK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

tK Group.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16Abl... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16Ack.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16ALK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16BTK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16EGFR.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Ephrins... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17FAK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17FGFR.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17FLT3.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18IRs.and.IGFRs.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18ITK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18JAK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18MET.Receptor... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19PDGFR.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19Src.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19Syk.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19Trk.Receptors... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19VEGFR.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20Other.RTKs.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20Multi-TK.Inhibitors... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

tKL Group .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21BMP.and.Other.Activin.Receptors... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21LIMK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21LRRK2.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21Raf... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21RIPK1.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22TAK1.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22TGF-β.Receptors... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

other Protein Kinases.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23Aurora.Kinase.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23CAMKK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23Haspin.Kinase.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23IKK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24Mps1.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24PERK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24PLK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

atyPiCaL and LiPid Kinases

atypical Kinases.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25ATM/ATR.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25DNA-PK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25eEF-2.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25mTOR.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Lipid Kinases.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27CerK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27DGK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27PI.3-kinase.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27SphK.... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

otHer

Broad spectrum Kinase inhibitors.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

Phosphatases.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Kinase inhibitor Classification.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

ContentsThis listing contains over 300 products from Tocris, including a wide range of protein kinase inhibitors divided into their respective kinome groups: AGC, CAMK, CK1, CMGC, STE, TK and TKL. Atypical, lipid and broad spectrum kinase inibitors are also listed, alongside phosphatase inhibitors.

KINASES

www.tocris.com | 3

KitFLT3

PDGFR

TK Group

TKL Group

AGC Group

CAMK Group

CMGC Group

STE Group

CK1 GroupOther Kinases

CSFR/FmsFGFR

METTrk

DDR1

IGF1R

Ack

SykFAKEphB4

EphA4Src

Fyn

Fgr

Lyn

Lck

AblBTK

ITK

EGFRRIPK1

LIMKTAK1

Raf1

ASK1

CK1

PAK

MEK

LRRK2

ALK4

ALK7

TGFβR1

BMPR1

ALK2

CK2

PERK

TTK/Mps1

DYRK

Clk

GSK-3

Cdk

ERK

p38 JNK

ALK1

JAKIR

ALK

PDK

Chk1

CAMKK

IKK

PLK

Haspin

Wee1

Aur

PimMLCK

DAPK

STK33

SIK

NUAKAMPK

MNK

CaMK II

ChK2PKD

MSK

RSK

SGK Akt/PKB

PKC

PKAROCK

PKG

IntroductionKinases are enzymes that catalyze the phosphorylation of target substrates. There are over 500 known kinases, which mediate a wide range of signal transduction pathways and control complex cellular functions. Kinases can be classified according to their structural and functional relationships, as represented by the ‘Human Kinome’.

Adapted from Manning et al (2002) Science 298 1912.

A Representation of the Human Kinome Featuring Kinases Targeted by Tocris Products

Kinome abbreviationsabl, Abelson murine leukemia viral oncogene; ack, activated Cdc42 kinase; akt/PKB, protein kinase B; aLK (TK group), anaplastic lymphoma kinase; aLK (TKL Group), activin receptor-like kinase; aMPK, AMP-activated protein kinase; asK, apoptosis signal-regulated kinase 1; aur, Aurora kinase; BMPr1, bone morphogenetic protein receptor 1; BtK, Bruton’s tyrosine kinase; CaMK ii, calmodulin-dependent kinase 2; CaMKK, calmodulin-dependent kinase kinase; Cdk, cyclin-dependent kinase; Chk, checkpoint kinase; CK1, casein kinase 1; CK2, casein kinase 2; Clk, Cdc2-like kinase; CsFr/Fms, colony stimulating factor receptor; daPK, death-associated protein kinase; ddr1, discoidin domain receptor tyrosine kinase 1; dyrK, dual-specificity tyrosine phosphorylation-regulated kinase; eGFr, epidermal growth factor receptor; epha4, ephrin A4; ephB4, ephrin B4; erK, extracellular signal-regulated kinase; FaK, focal adhesion kinase; FGFr, fibroblast growth factor receptor; FLt3, Fms-like receptor tyrosine kinase 3; GsK-3, glycogen synthase kinase 3; iGF1r, insulin-like growth factor 1 receptor; iKK, IκB kinase; ir, insulin receptor; itK, IL-2-inducible T cell kinase; JaK, Janus kinase; JnK, c-Jun N-terminal kinase; Kit, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; LiMK, LIM domain kinase; LrrK2, leucine-rich repeat kinase 2; MeK, mitogen-activated protein kinase kinase; MLCK, myosin light chain kinase; MnK, mitogen-activated protein kinase interacting protein kinase; MsK, mitogen- and stress-activated protein kinase; p38, p38 mitogen-activated protein kinase; PaK, p21-activated kinase; PdGFr, platelet-derived growth factor receptor; PdK, phosphoinositide-dependent kinase; PerK, PKR-like ER kinase; PKa, protein kinase A; PKC, protein kinase C; PKd, protein kinase D; PKG, protein kinase G; PLK, polo-like kinase; riPK1, receptor-interacting protein kinase 1; roCK, Rho-kinase; rsK, ribosomal S6 protein kinase; sGK, serum- and glucocorticoid-regulated kinase; siK, salt inducible kinase; stK33, serine/threonine kinase 33; syk, spleen tyrosine kinase; taK1, transforming growth factor-β-activated kinase 1; tGFβr1, transforming growth factor-β receptor 1; trk, neurotrophic tyrosine kinase receptor; ttK/Mps1, monopolar spindle 1


4 |

AGC GroupThe AGC group is named after three of its substituents – cAMP-dependent (protein kinase A; PKA), c-GMP-dependent (PKG) and protein kinase C (PKC). Members of this group preferentially phosphorylate serine/threonine residues close to arginine and lysine, the basic residues.

Akt/PKB (Protein Kinase B)

Activators 4635 SC 79 Akt activator 10 mg

50 mg

Inhibitors 3897 API-1 Selective Akt/PKB inhibitor; antitumor 10 mg

2151 API-2 Selective inhibitor of Akt/PKB signaling; antitumor and antiviral 10 mg

2558 10-DEBC hydrochloride Selective Akt/PKB inhibitor 10 mg

50 mg

2926 FPA 124 Akt/PKB inhibitor 10 mg

50 mg

4144 GSK 690693 Akt kinase inhibitor; antitumor 10 mg

50 mg

4598 PHT 427 Dual Akt and PDK1 inhibitor; antitumor 10 mg

50 mg

MSK (Mitogen- and Stress-activated Protein Kinase)

Inhibitors 4630 SB 747651A dihydrochloride Potent MSK1 inhibitor; also inhibits other AGC group kinases 10 mg

PDK1 (Phosphoinositide-dependent Kinase 1)

Activators 4087 PS 48 PDK1 activator 10 mg

50 mg

Inhibitors 3606 BAG 956 Dual PDK1 and PI 3-kinase inhibitor 10 mg

50 mg

4318 BX 795 PDK1 inhibitor 10 mg

50 mg

4143 GSK 2334470 Potent and selective PDK1 inhibitor 10 mg

50 mg

4598 PHT 427 Dual PDK1 and Akt inhibitor; antitumor 10 mg

50 mg

PKA (Protein Kinase A)

Activators 1140 8-Bromo-cAMP, sodium salt Cell permeable cAMP analog; activates PKA 10 mg

50 mg

1333 cAMPS-Sp, triethylammonium salt Cell permeable cAMP analog; activates PKA 1 mg

Inhibitors 1337 cAMPS-Rp, triethylammonium salt cAMP antagonist; inhibits PKA activation 1 mg

2910 H 89 dihydrochloride PKA inhibitor 1 mg

10 mg

50 mg

1288 KT 5720 Selective PKA inhibitor 100 µg

1904 PKA inhibitor fragment (6-22) amide

Potent PKA inhibitor 1 mg

2546 PKI 14-22 amide, myristoylated Cell-permeable PKA inhibitor 1 mg

PKC (Protein Kinase C)

Activators 2383 Bryostatin 1 High affinity PKC activator 10 µg

5237 Bryostatin 2 PKC activator; analog of Bryostatin 1 (Cat. No. 2383) 10 µg

5238 Bryostatin 3 Potent PKC activator 10 µg

3091 FR 236924 Selective PKCε activator 10 mg

4054 PEP 005 PKC activator 1 mg

4153 Phorbol 12,13-dibutyrate PKC activator 1 mg

1201 Phorbol 12-myristate 13-acetate PKC activator 1 mg

5 mg

1790 Pseudo RACK1 PKC activator peptide (attached to cell permeable vector) 1 mg

Category Cat. No. Product Name Description Unit Size

KINASES

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AGC Group – continued

Featured AGC Group Products

SC 79 (4635)Akt activator

O

OEt

NH2

Cl

OCN

EtO

O

SB 747651A dihydrochloride (4630)Potent MSK1 inhibitor; also inhibits other AGC group kinases

N N

N

N O

N

H2NHN

2HCl

HN

GSK 2334470 (4143)Potent and selective PDK1 inhibitor

NO

NH NN

NHMe

NH

N

NH2

KT 5720 (1288)Selective PKA inhibitor

GF 109203X (0741)PKC inhibitor

HN OO

NH

NMe2N

LY 333531 hydrochloride (4738)PKC inhibitor; selective for β isozymes

NN

HNO O

ON

HCl

NN

NH

OH Me

O

HOO

O

Featured AGC Group Activators and Inhibitors

Inhibitors 4128 Bisindolylmaleimide II Potent PKC inhibitor; also nicotinic receptor antagonist 10 mg

50 mg

1626 Calphostin C Potent, selective and photo-dependent PKC inhibitor 100 µg

2442 CGP 53353 Selective inhibitor of PKCβII 10 mg

1330 Chelerythrine chloride Cell-permeable PKC inhibitor 5 mg

0741 GF 109203X PKC inhibitor 1 mg

10 mg

2253 Go 6976 Potent PKC inhibitor; selective for α and β isozymes 1 mg

2285 Go 6983 Broad spectrum PKC inhibitor 1 mg

10 mg

2287 K-252c PKC inhibitor 1 mg

4738 LY 333531 hydrochloride PKC inhibitor; selective for β isozymes 1 mg

0609 (±)-Palmitoylcarnitine chloride PKC inhibitor 50 mg

4058 PKC (19-36) Pseudosubstrate peptide; inhibitor of PKC 1 mg

2992 PKC 412 PKC inhibitor 1 mg

1792 PKC β pseudosubstrate Selective PKC inhibitor peptide (attached to vector); cell-permeable

1 mg

1791 PKC ζ pseudosubstrate PKC ζ inhibitor peptide (attached to cell-permeable vector) 1 mg

1587 Ro 32-0432 hydrochloride Potent PKC inhibitor; orally active 1 mg

1610 Rottlerin Reported PKCδ inhibitor 10 mg

50 mg

2549 ZIP Cell-permeable inhibitor of atypical PKC isozyme PKMζ 1 mg

3290 ZIP, Biotinylated Biotinylated peptide for ZIP (Cat. No. 2549) 1 mg

3215 ZIP (Scrambled) Control peptide for ZIP (Cat. No. 2549) 1 mg

PKG (Protein Kinase G)

Inhibitors 1289 KT 5823 Selective PKG inhibitor 100 µg

3028 Rp-8-Br-PET-cGMPS PKG inhibitor 560 µg



6 |

AGC Group – continued

RSK2 in Complex with SL 0101-1Crystal Structure of RSK2 in Complex with the RSK2 Inhibitor SL 0101-1

Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 3UBD Utepbergenov et al (2012) Biochemistry 51 6499. PMID 22846040.

•...SL.0101-1.is.ATP-competitive.and.binds.to.a.unique.adenosine-interacting.loop.in.the.N-terminal.kinase.domain.of.RSK2

•. .SL.0101-1.is.a.potent.and.selective.RSK2.inhibitor.(IC50.=.89.nM)

•. .The.compound.selectively.inhibits.MCF-7.breast.cancer.cell.growth,.whilst.having.no.effect.on.normal.breast.cell.lines

Cat. No. 2250

CK1 Crystal Structure

CMGC Crystal StructureTKL Crystal Structure

STE Crystal Structure

AGC Crystal Structure TK Crystal Structure

HN

N

O

N

N

HO

N

NN

N

N

H2N

F

2HCl

OO

HO

OH

OH

OO

MeAcO

AcO

HO

S

N

O OH

N

N

N

N

NH

O

2HCl

Cl Cl

F

ON

H2N

NN

NH

Crystal structure analysis of protein-ligand complexes has become an essential technique in drug development. Structure based drug design enables the study of specific interactions between drug and target protein, and can result in inhibitors with optimized binding affinity and selectivity. This listing contains crystal structures of kinase inhibitors in complex with their target kinases, along with information regarding protein-ligand binding interactions. Chemical structures have been adapted to adopt the orientation of the ligand within the crystal structure.

ROCK (Rho-kinase)

Inhibitors 4927 AS 1892802 Potent ROCK inhibitor; orally bioavailable 10 mg

50 mg

0541 Fasudil hydrochloride ROCK inhibitor; also inhibits PKA 10 mg

50 mg

2485 Glycyl-H 1152 dihydrochloride Selective ROCK inhibitor; more selective analog of H 1152 dihydrochloride (Cat. No. 2414)

1 mg

4009 GSK 269962 Potent and selective ROCK inhibitor 10 mg

50 mg

3726 GSK 429286 Selective ROCK inhibitor 1 mg

10 mg

50 mg

2414 H 1152 dihydrochloride Selective ROCK inhibitor 1 mg

5061 RKI 1447 dihydrochloride Potent and selective ROCK inhibitor; antitumor 10 mg

50 mg

4118 SB 772077B dihydrochloride Potent ROCK inhibitor; vasodilator 10 mg

50 mg

3667 SR 3677 dihydrochloride Potent, selective ROCK inhibitor 10 mg

50 mg

1254 Y-27632 dihydrochloride Selective p160ROCK inhibitor 1 mg

10 mg

50 mg

RSK (Ribosomal S6 Protein Kinase)

Inhibitors 4037 BRD 7389 p90 RSK inhibitor 10 mg

50 mg

4032 PF 4708671 S6K1 inhibitor 10 mg

50 mg

2250 SL 0101-1 Selective p90 RSK inhibitor 1 mg

SGK (Serum- and Glucocorticoid-regulated Kinase)

Inhibitors 3572 GSK 650394 Selective SGK inhibitor 10 mg

50 mg


KINASES

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CAMK GroupThe CAMK group of protein kinases contains kinases that are primarily regulated by calcium/calmodulin signaling. Members include calcium/calmodulin-dependent protein kinase (CaMK), AMPK and Pim kinase. Like AGC kinases, these kinases tend to modify substrates containing basic residues.

Featured AMPK Activators and Inhibitors

A 769662 (3336)Potent AMPK activator

SNH

OH

O

HOCN

Dorsomorphin dihydrochloride (3093)Potent and selective AMPK inhibitor

N

NN

N

ON

2HCl

Featured AMPK Activators and Inhibitors

AMPK (AMP-activated Protein Kinase)

Activators 3336 A 769662 Potent AMPK activator 10 mg

50 mg

2840 AICAR AMPK activator; cell permeable 50 mg

3713 Cryptotanshinone AMPK activator; displays multiple other activities 10 mg

50 mg

2864 Metformin hydrochloride Activator of LKB1/AMPK; antidiabetic agent 100 mg

4039 PT 1 AMPK activator 10 mg

50 mg

5138 RSVA 405 AMPK activator; also STAT3 inhibitor 10 mg

50 mg

5285 ZLN 024 hydrochloride Allosteric AMPK activator 10 mg

50 mg

Inhibitors 3093 Dorsomorphin dihydrochloride Potent and selective AMPK inhibitor 10 mg

50 mg

CaMK II (Calmodulin-dependent Kinase II)

Inhibitors 2457 Arcyriaflavin A Potent CaMK II and cdk4/cyclin D1 inhibitor; antiviral agent 10 mg

1688 Autocamtide-2-related inhibitory peptide

Selective CaMK II inhibitor 1 mg

1277 KN-62 CaMK II inhibitor; also P2X7 antagonist 1 mg

1278 KN 93 CaMK II inhibitor; also K+ channel blocker (KV) 1 mg

5215 KN 93 phosphate CaMK II inhibitor; water soluble version of KN 93 (Cat. No. 1278)

1 mg

Chk (Checkpoint Kinase)

Inhibitors 5199 AZD 7762 hydrochloride Potent and selective Chk1 and Chk2 inhibitor 10 mg

50 mg

3034 NSC 109555 ditosylate Selective Chk2 inhibitor 10 mg

50 mg

2694 PD 407824 Selective inhibitor of Chk1 and Wee1 1 mg

10 mg

4277 PF 477736 Selective Chk1 inhibitor 10 mg

50 mg

2560 SB 218078 Chk1 inhibitor 1 mg

10 mg

3038 TCS 2312 Potent Chk1 inhibitor 1 mg



8 |

CAMK Group – continued

Featured CAMK Group Products

ETP 45835 dihydrochloride (5183)Mnk1 and Mnk2 inhibitor

HNN

HN

N2HCl

WZ 4003 (5177)Potent and selective NUAK1/2 inhibitor

NH

O

N

N

N

NCl

O

NH

O

MRT 67307 dihydrochloride (5134)SIK inhibitor

HNN

O

N

N N

HNH

O

2HCl

Featured CAMK Group Inhibitors

DAPK (Death-associated Protein Kinase)

Inhibitors 4301 TC-DAPK 6 Potent and selective inhibitor of DAPK1 10 mg

50 mg

MK2 (MAPK-activated Protein Kinase 2)

Inhibitors 4279 PF 3644022 Potent MK2 inhibitor 10 mg

3140 PHA 767491 hydrochloride MK2 inhibitor; also inhibits cdc7/cdk9 10 mg

50 mg

MLCK (Myosin Light Chain Kinase)

Inhibitors 4310 ML 7 hydrochloride Selective inhibitor of MLCK 10 mg

50 mg

0431 ML 9 hydrochloride MLCK inhibitor 10 mg

50 mg

1885 MLCK inhibitor peptide 18 Selective inhibitor of MLCK 1 mg

0369 W-7 hydrochloride MLCK inhibitor; also calmodulin antagonist 100 mg

MNK (MAPK-interacting Kinase)

Inhibitors 4500 Cercosporamide Potent Mnk2 inhibitor 500 µg

2731 CGP 57380 Selective inhibitor of Mnk1 1 mg

10 mg

50 mg

5183 ETP 45835 dihydrochloride Mnk1 and Mnk2 inhibitor 10 mg

50 mg

NUAK

Inhibitors 5177 WZ 4003 Potent and selective NUAK1/2 inhibitor 10 mg

50 mg

Pim Kinase

Inhibitors 3589 PIM-1 Inhibitor 2 Pim-1 kinase inhibitor 10 mg

50 mg

2979 TCS PIM-1 1 Selective, ATP-competitive Pim-1 kinase inhibitor 10 mg

50 mg

PKD (Protein Kinase D)

Inhibitors 4644 CID 2011756 Pan PKD inhibitor; cell permeable 10 mg

50 mg

3327 CID 755673 Selective PKD inhibitor 10 mg

4975 CRT 0066101 Potent PKD inhibitor 10 mg

3962 kb NB 142-70 Selective PKD inhibitor; analog of CID 755673 (Cat. No. 3327)

10 mg

50 mg

SIK (Salt Inducible Kinase)

Inhibitors 5134 MRT 67307 dihydrochloride SIK inhibitor 10 mg

50 mg

STK33 (Serine/Threonine Kinase 33)

Inhibitors 4880 ML 281 STK33 inhibitor 10 mg

50 mg


KINASES

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CK1 GroupThe casein kinase 1 (CK1) family is a small group of serine/threonine kinases that play an important role in a variety of signal transduction pathways, including Wnt signaling, DNA repair and control of cell differentiation and proliferation. Dysregulation of CK1 has been linked to cancer, Alzheimer’s and Parkinson’s disease.

Featured CK1 Group Kinases

LH 846 (4896)Selective CK1δ inhibitor

N

SHN

OCl

D 4476 (2902)Selective CK1 inhibitor; also inhibits TGF-βRI

NH

N

N

O

NH2

O

O

PF 4800567 hydrochloride (4281)Selective CK1ε inhibitor

N

N

NN

NH2

O

O

HCl

Cl

Featured CK1 Group Inhibitors

CK1δ in Complex with PF 670462Crystal Structure of CK1δ in Complex with the CK1ε/δ Inhibitor PF 670462

Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 3UZP Long et al (2012) J.Med.Chem. 55 956. PMID 22168824.

•...PF.670462.binds.to.the.ATP.binding.pocket.of.CK1.and.forms.strong.hydrophobic.interactions.with.Met80.and.Met82.side.chains.

•...PF.670462.is.a.potent.and.selective.CK1ε/δ.inhibitor.(IC50.values.are.7.7.and.14.nM.respectively)

•...The.compound.attenuates.methamphetamine-stimulated.locomotion.in vivo.

Cat. No. 3316





HN

N

O

N

N

HO

N

NN

N

N

H2N

F

2HCl

OO

HO

OH

OH

OO

MeAcO

AcO

HO

S

N

O OH

N

N

N

N

NH

O

2HCl

Cl Cl

F

ON

H2N

NN

NH

CK1 (Casein Kinase 1)

Inhibitors 5329 CKI 7 dihydrochloride CK1 inhibitor 10 mg

50 mg

3605 (R)-CR8 CK1 inhibitor; also inhibits cdk1/cdk5 10 mg

50 mg

2902 D 4476 Selective CK1 inhibitor; also inhibits TGF-βRI 10 mg

50 mg

3610 (R)-DRF053 dihydrochloride Dual CK1/cdk inhibitor 10 mg

50 mg

4896 LH 846 Selective CK1δ inhibitor 10 mg

50 mg

4281 PF 4800567 hydrochloride Selective CK1ε inhibitor 10 mg

50 mg

3316 PF 670462 Potent and selective CK1ε and CK1δ inhibitor 10 mg

50 mg



10 |

CMGC GroupCMGC kinases include: cyclin-dependent kinases (Cdks); mitogen-activated protein kinases (MAPKs); glycogen synthase kinase 3 (GSK-3); and Cdc2-like kinases (Clks), all of which are key components of signaling cascades. The MAPK pathway in particular is one of the best-studied mammalian signaling cascades.

Cdk (Cyclin-dependent Kinase)

Inhibitors 2072 Aminopurvalanol A Cdk inhibitor 10 mg

50 mg

2457 Arcyriaflavin A Potent cdk4/cyclin D1 and CaM kinase II inhibitor; antiviral agent

10 mg

3968 AZD 5438 Potent cdk1, cdk2 and cdk9 inhibitor 10 mg

50 mg

3605 (R)-CR8 Dual cdk1/cdk5 inhibitor; also inhibits CK1 10 mg

50 mg

3610 (R)-DRF053 dihydrochloride Dual cdk/CK1 inhibitor 10 mg

50 mg

1398 Kenpaullone Potent cdk inhibitor; also inhibits GSK-3 10 mg

2152 NSC 625987 Cdk4 inhibitor 10 mg

50 mg

3135 NU 2058 Cdk1 and cdk2 inhibitor 10 mg

50 mg

3301 NU 6140 Cdk2 inhibitor 10 mg

50 mg

1284 Olomoucine Cdk inhibitor 5 mg

25 mg

4786 PD 0332991 isethionate Potent, selective cdk4/6 inhibitor; brain penetrant 10 mg

50 mg

3140 PHA 767491 hydrochloride Dual cdk9/cdc7 inhibitor; also inhibits MK2 10 mg

50 mg

1580 Purvalanol A Cdk inhibitor 10 mg

50 mg

1581 Purvalanol B Cdk inhibitor 10 mg

50 mg

4181 Ro 3306 Cdk1 inhibitor 10 mg

50 mg

2609 Ryuvidine Cdk4 inhibitor; also SETD8 inhibitor 10 mg

50 mg

4875 Senexin A Cdk8 inhibitor 10 mg

4075 SNS 032 Potent cdk2, cdk7 and cdk9 inhibitor 10 mg

50 mg

2907 SU 9516 Potent cdk2 inhibitor 10 mg

50 mg

CK2 (Casein Kinase 2)

Inhibitors 2275 TBB Selective CK2 inhibitor; cell-permeable 10 mg

50 mg

4432 TTP 22 High affinity, selective CK2 inhibitor 10 mg

50 mg

Clk (Cdc2-like Kinase)

Inhibitors 4336 TG 003 Potent, ATP-competitive inhibitor of Clk-family kinases 10 mg

50 mg

DYRK (Dual-specificity Tyrosine Phosphorylation-regulated Kinase)

Inhibitors 5075 Harmine Potent and selective DYRK1A inhibitor 50 mg

4997 INDY DYRK1A/B inhibitor 10 mg

4998 ProINDY DYRK1A/B inhibitor; prodrug of INDY (Cat. No. 4997) 10 mg


KINASES

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CMGC Group – continued

Senexin A (4875)Cdk8 inhibitor

N

N

NC

HN

HCl

Featured CMGC Group Products - part 1

CHIR 99021 (4423)Highly selective GSK-3 inhibitor

N

N

HN

N

HN

HN

NCN

ClCl

SB 216763 (1616)Potent, selective GSK-3 inhibitor

HN

NMe

OO

Cl

Cl

Featured CMGC Group Inhibitors

ERK (Extracellular Signal-regulated Kinase)

Inhibitors 3706 FR 180204 Selective ERK inhibitor 10 mg

50 mg

4433 Pluripotin Dual ERK1/RasGAP inhibitor; maintains ESC self-renewal 1 mg

4465 TCS ERK 11e Potent and selective ERK2 inhibitor 10 mg

3675 TMCB Dual ERK8 and CK2 inhibitor 10 mg

50 mg

4132 XMD 8-92 Selective ERK5/BMK1 inhibitor 10 mg

50 mg

GSK-3 (Glycogen Synthase Kinase)

Inhibitors 4083 3F8 Potent and selective GSK-3β inhibitor 10 mg

50 mg

4431 A 1070722 Highly potent, selective GSK-3 inhibitor 10 mg

50 mg

3966 AR-A 014418 Selective GSK-3 inhibitor 10 mg

50 mg

3194 BIO Potent, selective GSK-3 inhibitor 10 mg

50 mg

3874 BIO-acetoxime Selective GSK-3α/β inhibitor 1 mg

10 mg

4423 CHIR 99021 Highly selective GSK-3 inhibitor 10 mg

50 mg

4953 CHIR 99021 trihydrochloride Hydrochloride salt of CHIR 99021 (Cat. No. 4423); selective GSK-3 inhibitor

10 mg

50 mg

2256 L803-mts Selective inhibitor of GSK-3 1 mg

1616 SB 216763 Potent, selective GSK-3 inhibitor 1 mg

10 mg

50 mg

1617 SB 415286 Potent, selective GSK-3 inhibitor 10 mg

50 mg

4353 TC-G 24 Potent and selective GSK-3β inhibitor 10 mg

50 mg

3869 TCS 2002 Potent GSK-3β inhibitor 10 mg

50 mg

4221 TCS 21311 Potent GSK-3β inhibitor; also inhibits JAK3 and PKC 10 mg

50 mg

3835 TWS 119 GSK-3β inhibitor; induces neuronal differentiation in ESCs 10 mg



12 |

Featured CMGC Group Products - part 2

TCS JNK 6o (3222)Selective JNK inhibitor

N

CN

OEt

NH2

NH

O

OMe

OMe

AL 8697 (4753)Potent and selective p38α inhibitor

NN

N

FNH

O

F F

DBM 1285 dihydrochloride (5095)p38 MAPK inhibitor; anti-inflammatory

N

S

HN

N

N

F

NH2HCl

SB 203580 (1202)Selective inhibitor of p38 MAPK

N

HN

S

Me

O

N

F

SB 706504 (5040)p38 MAPK inhibitor

N

N NHN

NH

NH

NH

NC

F F

F

O

Featured MAPK Signaling Inhibitors

JNK (c-Jun N-terminal Kinase)

Activators 1290 Anisomycin JNK, SAPK and p38 activator 10 mg

50 mg

Inhibitors 2651 AEG 3482 Inhibitor of JNK signaling 10 mg

50 mg

3314 BI 78D3 Selective, competitive JNK inhibitor 10 mg

50 mg

4924 CEP 1347 Inhibitor of JNK signaling; neuroprotective 1 mg

1989 c-JUN peptide Peptide inhibitor of JNK/c-Jun interaction 1 mg

4550 IQ 3 Selective JNK3 inhibitor 10 mg

50 mg

1496 SP 600125 Selective JNK inhibitor 10 mg

50 mg

5044 SR 3576 Highly potent and selective JNK3 inhibitor 10 mg

50 mg

3607 SU 3327 Selective JNK inhibitor 10 mg

50 mg

2827 TCS JNK 5a Selective inhibitor of JNK2 and JNK3 10 mg

50 mg

3222 TCS JNK 6o Selective JNK inhibitor 10 mg

50 mg


KINASES

www.tocris.com | 13

CMGC Group – continued

DYRK1A in Complex with INDYCrystal Structure of DYRK1A in Complex with the DYRK1A/B Inhibitor INDY

Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 3ANQ Ogawa et al (2010) Nat.Commun. 1 86. PMID 20981014.

•. .INDY.binds.at.the.ATP.binding.cleft.of.DYRK1A,.as.well.as.forming.extensive.hydrophobic.interactions.with.Val173,.Ala186,.Phe238,.Leu241,.Leu294.and.Val306

•. .INDY.is.a.DYRK1A/B.inhibitor.(IC50.values.are.240.and.230.nM.respectively)

•. .The.compound.impairs.self-renewal.capacity.of.subventricular.zone.neural.stem.cells

Cat. No. 4997





HN

N

O

N

N

HO

N

NN

N

N

H2N

F

2HCl

OO

HO

OH

OH

OO

MeAcO

AcO

HO

S

N

O OH

N

N

N

N

NH

O

2HCl

Cl Cl

F

ON

H2N

NN

NH

p38 MAPK

Inhibitors 4753 AL 8697 Potent and selective p38α inhibitor 10 mg

50 mg

2186 CMPD-1 Non-ATP-competitive p38α inhibitor 10 mg

50 mg

5095 DBM 1285 dihydrochloride p38 MAPK inhibitor; anti-inflammatory 10 mg

50 mg

2908 EO 1428 Selective inhibitor of p38α and p38β2 10 mg

50 mg

2657 JX 401 Potent, reversible p38α inhibitor 10 mg

50 mg

4586 ML 3403 p38 inhibitor 10 mg

50 mg

2999 RWJ 67657 Potent, selective p38α and p38β inhibitor 10 mg

1264 SB 202190 Potent, selective inhibitor of p38 MAPK 10 mg

50 mg

1202 SB 203580 Selective inhibitor of p38 MAPK 1 mg

10 mg

50 mg

1402 SB 203580 hydrochloride Selective inhibitor of p38 MAPK; water-soluble 10 mg

1962 SB 239063 Potent, selective p38 MAPK inhibitor; orally active 10 mg

5040 SB 706504 p38 MAPK inhibitor 10 mg

50 mg

3528 SCIO 469 hydrochloride Selective p38 MAPK inhibitor 10 mg

50 mg

2008 SKF 86002 dihydrochloride p38 MAPK inhibitor; anti-inflammatory agent 10 mg

50 mg

4254 TAK 715 Potent p38 MAPK inhibitor; anti-inflammatory 10 mg

50 mg

3916 VX 702 Orally active p38α and p38β inhibitor 10 mg

3915 VX 745 Potent and selective p38α inhibitor 10 mg

50 mg

SRPK (Serine Arginine Protein Kinase)

Inhibitors 5063 SRPIN340 Selective SRPK1 inhibitor 10 mg

50 mg



14 |

STE GroupSTE (homologs of yeast sterile 7, sterile 11, sterile 20) kinases are so named because of their homology with yeast MAPKs. MEK, a STE7 kinase that phosphorylates MAPKs, is itself phosphorylated by members of the STE11 group (including ASK); the STE11 group may in turn be phosphorylated by STE20 kinases (e.g. PAK).

Potent PAK Inhibitor

FraX 486 Cat. No. 5190

FRAX.486.is.a.potent.p21-activated.kinase.(PAK).inhibitor.(IC50.values.are.14,.33,.39.and.575.nM.for.PAK1,.PAK2,.PAK3.and.PAK4.respectively),.that.blocks.and.reverses.DISC1.knockdown-induced.reduction.in.dendritic.spine.size.in.cortical.neurons..The.compound.also.attenuates.dendritic.spine.elimination.and.enhances.spine.generation.in.DISC1.knockdown.mice..FRAX.486.is.brain.penetrant.and.orally.bioavailable.

Potent PAK InhibitorFRAX 486 (5190)

HN

N

FHN

N

N

N

Cl

ClO

ASK (Apoptosis Signal-regulated Kinase 1)

Inhibitors 4429 NQDI 1 ASK1 inhibitor 10 mg

50 mg

4825 TC ASK 10 Potent and selective ASK1 inhibitor; orally bioavailable 10 mg

50 mg

MEK (Mitogen-activated Protein Kinase Kinase)

Inhibitors 1777 Arctigenin Potent MEK1 inhibitor; also inhibits IκBα phosphorylation 10 mg

50 mg

4842 BIX 02189 Selective MEK5 and ERK5 inhibitor 10 mg

50 mg

4192 PD 0325901 Potent inhibitor of MEK1/2 10 mg

50 mg

4237 PD 184352 Selective MEK inhibitor 10 mg

50 mg

2605 PD 198306 Selective inhibitor of MEK1/2 10 mg

4824 PD 334581 MEK1 inhibitor 10 mg

50 mg

1213 PD 98059 MEK inhibitor 1 mg

10 mg

50 mg

1969 SL 327 Selective inhibitor of MEK1 and MEK2; brain penetrant 1 mg

10 mg

50 mg

1868 U0124 Inactive analog of U0126 (Cat. No. 1144) 10 mg

1144 U0126 Potent, selective inhibitor of MEK1/2 5 mg

25 mg

PAK (p21-activated Kinase)

Inhibitors 5190 FRAX 486 Potent PAK inhibitor; brain penetrant and orally bioavailable 10 mg

50 mg

3622 IPA 3 Group I PAK inhibitor 10 mg

50 mg

4212 PIR 3.5 Negative control of IPA 3 (Cat. No. 3622) 10 mg

50 mg


KINASES

www.tocris.com | 15

Featured STE Group Products

BIX 02189 (4842)Selective MEK5 and ERK5 inhibitor

PD 0325901 (4192)Potent inhibitor of MEK1/2

HN

F

IF

F

HN

OHOO

OH

NH

O

NH

O

N

N

NH2

S

H2N

CN

NC

NH2

S

H2N

NH

O

O

EtO2C

U0126 (1144)Potent, selective inhibitor of MEK1/2

NQDI 1 (4429)ASK1 inhibitor

Featured STE Group Inhibitors

STE Group – continued

ASK1 in Complex with TC ASK 10Crystal Structure of ASK1 in Complex with the Inhibitor TC ASK 10

Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 3VW6 Terao et al (2012) Bioorg.Med.Chem.Lett. 22 7326. PMID 23147077.

•. .TC.ASK.10.forms.two.hydrogen.bonds.with.the.hinge.region.of.ASK1.and.also.interacts.with.the.side.chain.of.Lys709

•. .TC.ASK.10.is.a.potent.and.selective.ASK.inhibitor.(IC50.=.14.nM)

•. The.compound.is.orally.available





HN

N

O

N

N

HO

N

NN

N

N

H2N

F

2HCl

OO

HO

OH

OH

OO

MeAcO

AcO

HO

S

N

O OH

N

N

N

N

NH

O

2HCl

Cl Cl

F

ON

H2N

NN

NH

Cat. No. 4825


16 |

TK GroupMembers of the TK (tyrosine kinase) group exclusively phosphorylate tyrosine residues. Receptor and non-receptor tyrosine kinases including EGFR, FGFR, MET, PDGFR and Src kinases, are key members of this family. Receptor tyrosine kinases are particularly important therapeutic targets in cancer.

ALK in Complex with CrizotinibCrystal Structure of ALK in Complex with the Dual ALK/c-MET Inhibitor Crizotinib

Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 2XP2 Cui et al (2011) J.Med.Chem. 54 6342. PMID 21812414.

•. .Crizotinib.preferentially.binds.to.the.ATP.binding.pocket.of.ALK.in.its.inactive.conformation

•. .Crizotinib.is.a.potent.and.selective.c-MET/ALK.inhibitor.(IC50.values.are.8.and.20.nM.respectively)

•. .The.compound.inhibits.tumor.cell.growth.in.cell.lines.expressing.ALK.mutations.and.is.orally.bioavailable...

Cat. No. 4368





HN

N

O

N

N

HO

N

NN

N

N

H2N

F

2HCl

OO

HO

OH

OH

OO

MeAcO

AcO

HO

S

N

O OH

N

N

N

N

NH

O

2HCl

Cl Cl

F

ON

H2N

NN

NH

Abl

Inhibitors 3716 Adaphostin p210Bcr-Abl kinase inhibitor 10 mg

50 mg

4274 AP 24534 Potent multi-kinase and pan-Bcr-Abl inhibitor 10 mg

50 mg

4361 Bosutinib Dual Abl/Src inhibitor; antiproliferative 10 mg

50 mg

4399 GNF 2 Selective allosteric inhibitor of Bcr-Abl tyrosine kinase activity 10 mg

50 mg

4908 GNF 5 Selective allosteric inhibitor of Bcr-Abl; analog of GNF 2 (Cat. No. 4399)

10 mg

50 mg

4730 PPY A Potent inhibitor of Abl T315l mutant and wild-type Abl kinases

10 mg

50 mg

Ack (Activated Cdc42 Kinase)

Inhibitors 4946 AIM 100 Potent and selective Ack1 inhibitor 10 mg

50 mg

5098 KRCA 0008 Potent Ack1 and ALK dual inhibitor; orally bioavailable 10 mg

50 mg

ALK (Anaplastic Lymphoma Kinase)

Inhibitors 5310 ASP 3026 ALK inhibitor 10 mg

50 mg

4368 Crizotinib Potent ALK/c-MET inhibitor 10 mg

50 mg

5111 GSK 1838705 Potent ALK inhibitor; also IR and IGF1R inhibitor 10 mg

50 mg

5098 KRCA 0008 Potent ALK and Ack1 dual inhibitor; orally bioavailable 10 mg

50 mg

BTK (Bruton’s Tyrosine Kinase)

Inhibitors 1300 LFM-A13 Potent, selective BTK inhibitor 10 mg

50 mg

4710 PF 06465469 Potent BTK inhibitor; also inhibits interleukin-2 inducible T cell kinase (ITK)

10 mg

50 mg

1405 (-)-Terreic acid Selective inhibitor of BTK 10 mg


KINASES

www.tocris.com | 17

TK Group – continued

EGFR (Epidermal Growth Factor Receptor)

Inhibitors 1276 AG 1478 hydrochloride Highly potent EGFR-kinase inhibitor 10 mg

50 mg

0414 AG 490 EGFR-kinase inhibitor; also JAK2/3 inhibitor 10 mg

50 mg

2417 BIBU 1361 dihydrochloride Selective inhibitor of EGFR-kinase 1 mg

10 mg

2416 BIBX 1382 dihydrochloride Highly selective EGFR-kinase inhibitor 1 mg

10 mg

5022 BMS 599626 dihydrochloride Potent, selective EGFR and ErbB2 inhibitor 10 mg

3360 CGP 52411 EGFR inhibitor; also inhibits Aβ42 fibril formation 10 mg

50 mg

1110 Genistein EGFR-kinase inhibitor; also estrogen and PPARγ ligand 10 mg

50 mg

2239 GW 583340 dihydrochloride Potent dual EGFR/ErbB2 inhibitor; orally active 10 mg

50 mg

2646 HDS 029 Potent inhibitor of the ErbB receptor family 1 mg

10 mg

3580 HKI 357 Dual irreversible inhibitor of ErbB2 and EGFR 10 mg

50 mg

3000 Iressa Selective EGFR inhibitor; orally active 10 mg

50 mg

3352 JNJ 28871063 hydrochloride Potent ErbB receptor family inhibitor 10 mg

50 mg

1037 PD 153035 hydrochloride EGFR-kinase inhibitor 10 mg

50 mg

2615 PD 158780 Potent ErbB receptor family inhibitor 10 mg

50 mg

4941 PKI 166 hydrochloride Potent EGFR-kinase inhibitor 10 mg

2794 PP 3 EGFR-kinase inhibitor 10 mg

3599 TAK 165 Potent and selective ErbB2 inhibitor 10 mg

50 mg

3115 WHI-P 154 Potent EGFR inhibitor; also inhibits JAK3 10 mg

50 mg

Ephrins

Inhibitors 5290 KYL EphA4 receptor inhibitor; neuroprotective 1 mg

4405 NVP BHG 712 Potent EphB4 kinase inhibitor 1 mg

FAK (Focal Adhesion Kinase)

Inhibitors 3414 FAK Inhibitor 14 Selective FAK inhibitor 10 mg

50 mg

4278 PF 431396 Dual FAK/PYK2 inhibitor 10 mg

3239 PF 573228 Potent and selective FAK inhibitor 10 mg

50 mg

4498 Y 11 Potent and selective FAK inhibitor 10 mg

50 mg

FGFR (Fibroblast Growth Factor Receptor)

Inhibitors 4002 FIIN 1 hydrochloride Potent, irreversible FGFR inhibitor 10 mg

50 mg

3724 PD 161570 Selective FGFR inhibitor 10 mg

50 mg

3785 PD 166285 dihydrochloride FGFR1 inhibitor; also inhibits Src, PDGFRβ and Wee1 1 mg

10 mg

3044 PD 173074 FGFR1/3 inhibitor 10 mg

50 mg

3300 SU 5402 Potent FGFR and VEGFR inhibitor 1 mg

Other 4826 SUN 11602 Basic FGF (bFGF) mimetic; neuroprotective 10 mg

50 mg



18 |

Featured TK Group Inhibitors

BMS 509744 (5009)Potent and selective ITK kinase inhibitor

O

O

N

N

O

S

N

SHN

O

HN

KB SRC 4 (4660)Potent and selective c-Src inhibitor

N

N

NH2

N

NN

N

N

Cl

DDR1-IN-1 dihydrochloride (5077)Selective DDR1 inhibitor

NH

O

N

N

CF3

O

NH

O2HCl

Featured TK Group Inhibitors

FLT3 (Fms-like Receptor Tyrosine Kinase-3)

Inhibitors 4033 5ʹ-Fluoroindirubinoxime FLT3 inhibitor; displays antiproliferative activity 10 mg

50 mg

3395 Lestaurtinib JAK2, FLT3 and TrkA inhibitor 1 mg

2591 TCS 359 Potent FLT3 inhibitor 10 mg

50 mg

IRs and IGFRs (Insulin and Insulin-like Receptors)

Activators 1819 Demethylasterriquinone B1 Selective IR activator 5 mg

3435 Insulin (human) recombinant Endogenous peptide agonist 10 mg

Inhibitors 4774 BMS 536924 Dual IR/IGF1R inhibitor 10 mg

50 mg

5111 GSK 1838705 Potent IR and IGF1R inhibitor; also inhibits anaplastic lymphoma kinase (ALK)

10 mg

50 mg

5247 NVP ADW 742 ATP-competitive inhibitor of IGF1R 10 mg

50 mg

2956 Picropodophyllotoxin Selective IGF1R inhibitor 10 mg

2768 PQ 401 IGF1R inhibitor 10 mg

50 mg

ITK (IL-2-inducible T cell kinase)

Inhibitors 5009 BMS 509744 Potent and selective ITK kinase inhibitor 10 mg

JAK (Janus Kinase)

Inhibitors 4580 Atiprimod dihydrochloride JAK2 inhibitor 10 mg

4556 CP 690550 citrate Potent JAK inhibitor 10 mg

50 mg

1571 Cucurbitacin I Selective inhibitor of JAK2/STAT3 signaling 1 mg

4338 NSC 33994 JAK2 inhibitor 10 mg

50 mg

3035 SD 1008 JAK2/STAT3 signaling pathway inhibitor 10 mg

50 mg

3115 WHI-P 154 JAK3 kinase inhibitor; also inhibits EGFR 10 mg

50 mg

1367 ZM 39923 hydrochloride Potent, selective JAK3 inhibitor 10 mg

50 mg

1366 ZM 449829 Potent, selective JAK3 inhibitor 10 mg

50 mg


KINASES

www.tocris.com | 19



MET Receptor

Inhibitors 4368 Crizotinib Potent c-MET/ALK inhibitor 10 mg

50 mg

4239 PF 04217903 mesylate Highly selective c-MET inhibitor 10 mg

50 mg

2693 PHA 665752 Potent and selective MET inhibitor 10 mg

50 mg

4101 SU 11274 Selective inhibitor of MET kinase activity 10 mg

50 mg

PDGFR (Platelet-derived Growth Factor Receptor)

Inhibitors 1222 DMPQ dihydrochloride Potent, selective inhibitor of PDGFRβ 10 mg

50 mg

3304 SU 16f Potent and selective PDGFRβ inhibitor 10 mg

50 mg

Src

Activators 4582 MLR 1023 Selective allosteric activator of Lyn kinase 10 mg

50 mg

Inhibitors 3914 A 419259 trihydrochloride Inhibitor of Src family kinases 10 mg

3963 AZM 475271 Src kinase inhibitor 10 mg

50 mg

4361 Bosutinib Dual Src/Abl inhibitor; antiproliferative 10 mg

50 mg

4660 KB SRC 4 Potent and selective c-Src inhibitor 10 mg

50 mg

3063 1-Naphthyl PP1 Src family kinase inhibitor; also inhibits c-Abl 10 mg

50 mg

1554 Piceatannol p56lck and Syk kinase inhibitor 10 mg

1397 PP 1 Potent, selective Src family kinase inhibitor 10 mg

1407 PP 2 Potent, selective Src family kinase inhibitor 10 mg

2794 PP 3 Negative control for PP 2 (Cat. No. 1407) 10 mg

3642 Src I1 Dual site Src kinase inhibitor 10 mg

50 mg

Other 2265 Lyn peptide inhibitor Inhibits Lyn-dependent activities of IL-5 receptor; cell-permeable 1 mg

Syk (Spleen Tyrosine Kinase)

Inhibitors 2471 ER 27319 maleate Selective Syk kinase inhibitor 10 mg

50 mg

1554 Piceatannol Syk and p56lck kinase inhibitor 10 mg

Trk Receptors

Agonists 2837 BDNF (human) Activates TrkB and p75 receptors 10 µg

3826 7,8-Dihydroxyflavone TrkB agonist 10 mg

50 mg

4607 LM 22A4 Potent TrkB agonist 10 mg

50 mg

Antagonists 4781 ANA 12 TrkB receptor antagonist 10 mg

50 mg

5062 Cyclotraxin B TrkB receptor antagonist 1 mg

Inhibitors 4559 GNF 5837 Potent Trk inhibitor; inhibits TrkA, TrkB and TrkC 10 mg

50 mg

2238 GW 441756 Potent, selective TrkA inhibitor 10 mg

50 mg

Other 5046 LM11A 31 dihydrochloride Nonpeptide p75NTR ligand; neuroprotective 10 mg

50 mg

5101 PD 90780 Inhibits NGF binding to p75NTR 10 mg

50 mg

2272 Ro 08-2750 Inhibits NGF binding to p75NTR and TrkA 1 mg

10 mg

50 mg


20 |


Growth Factor Receptor Inhibitors

ASP 3026 (5310)Potent ALK inhibitor

HKI 357 (3580)Dual irreversible inhibitor of ErbB2 and EGFR

NEtO

CN

HNHN

O

O

Cl

F

NMe2

NVP ADW 742 (5247)ATP-competitive inhibitor of IGF1R

NN

N

O

NH2

N

SU 5416 (3037)VEGFR inhibitor; also inhibits KIT,

RET, MET and FLT3

NH

O

NH

Toceranib (3909)Potent PDGFR and VEGFR inhibitor

NH

O

NH

NH

O N

FN

N

N

OMeHN

N N

N

HN

SO

O

Featured Growth Factor Receptor Inhibitors


VEGFR (Vascular Endothelial Growth Factor)

Inhibitors 4350 Axitinib Potent VEGFR-1, -2 and -3 inhibitor 10 mg

50 mg

4471 DMH4 Selective VEGFR-2 inhibitor 10 mg

50 mg

2542 Ki 8751 Potent, selective VEGFR-2 inhibitor 10 mg

50 mg

3768 Sunitinib malate Potent VEGFR, PDGFRβ and KIT inhibitor 10 mg

50 mg

5422 XL 184 Potent VEGFR inhibitor; also inhibits other RTKs 10 mg

50 mg

2499 ZM 306416 hydrochloride VEGFR inhibitor 1 mg

10 mg

2475 ZM 323881 hydrochloride Potent, selective inhibitor of VEGFR-2 1 mg

10 mg

Other RTKs

Inhibitors 5077 DDR1-IN-1 dihydrochloride Selective DDR1 inhibitor 10 mg

50 mg

4481 Ki 20227 c-Fms inhibitor; suppresses osteolysis and osteoclast accumulation

10 mg

50 mg

5102 PLX 647 dihydrochloride Potent dual Fms/KIT inhibitor 10 mg

50 mg

Multi-TK Inhibitors

Inhibitors 5318 AEE 788 Potent EGFR and VEGFR inhibitor 10 mg

50 mg

2086 GTP 14564 Class III receptor tyrosine kinase (RTK) inhibitor 10 mg

4965 PD 180970 p210Bcr/Abl kinase inhibitor; also inhibits c-Src and KIT 10 mg

4885 R 1530 Multi-RTK inhibitor; inhibits angiogenesis 10 mg

50 mg

3037 SU 5416 VEGFR inhibitor; also inhibits KIT, RET, MET and FLT3 10 mg

50 mg

3335 SU 6668 PDGFR, VEGFR and FGFR inhibitor 10 mg

50 mg

3909 Toceranib Potent PDGFR and VEGFR inhibitor 10 mg

50 mg

KINASES

www.tocris.com | 21

TKL GroupThe TKL (tyrosine kinase-like) kinases include Raf kinase, BMP receptor and TGF-β receptor serine/threonine kinases. These enzymes exhibit sequence similarity to tyrosine kinases, but phosphorylate serine/threonine residues instead of tyrosine residues.

B-Raf in Complex with SB 590885Crystal Structure of B-Raf in Complex with the B-Raf Inhibitor SB 590885

Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 2FB8 King et al (2006) Cancer Res. 66 11100. PMID 17145850.

•. .SB.590885.binds.to.the.ATP.binding.pocket.of.B-Raf.in.its.active.conformation

•. .SB.590885.is.a.potent.and.selective.B-Raf.inhibitor.(Kd.=.0.3.nM)

•. .The.compound.inhibits.proliferation.of.tumor.cells.expressing.B-RafV600E





HN

N

O

N

N

HO

N

NN

N

N

H2N

F

2HCl

OO

HO

OH

OH

OO

MeAcO

AcO

HO

S

N

O OH

N

N

N

N

NH

O

2HCl

Cl Cl

F

ON

H2N

NN

NH

Cat. No. 2650

BMP and Other Activin Receptors

Inhibitors 4126 DMH-1 Selective ALK2 inhibitor 10 mg

50 mg

4986 K 02288 Type 1 BMP receptor inhibitor 10 mg

50 mg

4945 ML 347 Potent and selective ALK1 and ALK2 inhibitor 10 mg

50 mg

Other 4490 Alantolactone Antiproliferative; induces activin/SMAD3 signaling 10 mg

50 mg

LIMK

Inhibitors 4745 LIMKi 3 Potent LIM kinase inhibitor; antitumor 10 mg

5269 T 5601640 Selective LIMK2 inhibitor; antitumor 10 mg

50 mg

LRRK2 (Leucine-rich Repeat Kinase 2)

Inhibitors 4534 CZC 54252 hydrochloride Potent LRRK2 inhibitor; neuroprotective 10 mg

50 mg

4629 GSK2578215A Potent, selective LRRK2 inhibitor; brain penetrant 10 mg

50 mg

4273 LRRK2-IN-1 Potent and selective LRRK2 inhibitor 10 mg

50 mg

Raf

Inhibitors 4836 AZ 628 Potent Raf kinase inhibitor 10 mg

50 mg

4453 GDC 0879 Potent B-Raf inhibitor 10 mg

50 mg

1381 GW 5074 Potent, selective c-Raf1 kinase inhibitor 10 mg

50 mg

3185 L-779,450 Potent Raf kinase inhibitor 10 mg

50 mg

5036 ML 786 dihydrochloride Potent Raf kinase inhibitor; orally bioavailable 10 mg

2650 SB 590885 Potent B-Raf inhibitor 10 mg

50 mg

1321 ZM 336372 Potent, selective c-Raf inhibitor 10 mg

50 mg



22 |

Featured TKL Group Products

DMH-1 (4126)Selective ALK2 inhibitor

N

N N

O

N

K 02288 (4986)Type 1 BMP receptor inhibitor

N

NH2

OMe

MeO

MeO

OH

ML 347 (4945)Potent and selective ALK1 and ALK2 inhibitor

N

N N

O

N

LIMKi 3 (4745)Potent LIM kinase inhibitor; antitumor

NN

F

F

N

S

HN

O

Cl Cl

ML 786 dihydrochloride (5036)Potent Raf kinase inhibitor; orally bioavailable

HN

O

O

HN N ONH2

F3C2HCl

TKL Group Inhibitors

TKL Group – continued

RIPK1 (Receptor-interacting Protein Kinase 1)

Inhibitors 2324 Necrostatin-1 RIPK1 inhibitor; inhibits necroptosis 10 mg

50 mg

TAK1 (TGF-β-activated Kinase 1)

Inhibitors 3604 (5Z)-7-Oxozeaenol Potent and selective TAK1 MAPKKK inhibitor 1 mg

TGF-β Receptors (Transforming Growth Factor-β Receptors)

Inhibitors 2939 A 83-01 Selective inhibitor of TGF-βRI, ALK4 and ALK7 10 mg

50 mg

2902 D 4476 Selective TGF-βRI; also CK1 inhibitor 10 mg

50 mg

3264 GW 788388 Selective inhibitor of TGF-βRI; orally active 10 mg

50 mg

2718 LY 364947 Selective inhibitor of TGF-βRI 1 mg

10 mg

5288 R 268712 Potent and selective inhibitor of TGF-βRI 10 mg

50 mg

3742 RepSox Selective inhibitor of TGF-βRI; enhances cellular reprogramming efficiency

10 mg

50 mg

1614 SB 431542 Potent, selective inhibitor of TGF-βRI, ALK4 and ALK7 1 mg

10 mg

3263 SB 505124 Selective inhibitor of TGF-βRI, ALK4 and ALK7 10 mg

50 mg

3211 SB 525334 Selective inhibitor of TGF-βRI 10 mg

50 mg

3269 SD 208 Potent ATP-competitive TGF-βRI inhibitor 10 mg

50 mg

Other 5068 ITD 1 Selective inhibitor of TGF-β signaling; induces cardiomyocyte differentiation in ESCs

10 mg

50 mg


KINASES

www.tocris.com | 23

Other Protein Kinases The Other Protein Kinases group contains protein kinases that do not readily fit into the existing kinome categorization. Members include the Aurora kinases A, B and C; CAM kinase kinase (CAMKK); Polo-like kinase (PLK); and IκB kinase (IKK).

Featured Other Protein Kinase Inhiitors

TC-A 2317 hydrochloride (4066)Potent, selective Aurora kinase A inhibitor

N NH

NH

NC NHN

HO

HCl

TC-S 7010 (5286)Potent and selective Aurora

kinase A inhibitor

CHR 6494 trifluoroacetate (5326)Potent and selective haspin kinase inhibitor

NNH

N

N

N

NH

CF3CO2H

LDN 209929 dihydrochloride (4828)Potent and selective haspin kinase inhibitor

N

Cl OMe

S NH2

2HCl

Amlexanox (4857)Inhibitor of TBK1 and IKKε; antiallergic agent

O N

O

NH2

CO2H

TC Mps1 12 (4750)Potent and selective Mps1 kinase

inhibitor; orally active

NNH

CN

NH2

NH

H2N

O

N

N N

H

NH

OCl

F

HN

N

O

N

Featured Other Protein Kinase Inhibitors

Aurora Kinase

Inhibitors 4291 CCT 137690 Potent pan-Aurora kinase inhibitor 10 mg

50 mg

3988 Hesperadin hydrochloride Potent Aurora kinase B inhibitor 10 mg

50 mg

4821 PF 03814735 Aurora kinase A and B inhibitor 10 mg

50 mg

4584 SNS 314 mesylate Potent pan-Aurora kinase inhibitor 10 mg

50 mg

4066 TC-A 2317 hydrochloride Potent, selective Aurora kinase A inhibitor 10 mg

50 mg

5286 TC-S 7010 Potent and selective Aurora kinase A inhibitor 10 mg

50 mg

2458 ZM 447439 Inhibits Aurora kinase B 10 mg

CAMKK (Calmodulin-dependent Kinase Kinase)

Inhibitors 1551 STO-609 acetate Selective CAMKK inhibitor 1 mg

10 mg

50 mg

Haspin Kinase

Inhibitors 5326 CHR 6494 trifluoroacetate Potent and selective haspin kinase inhibitor 10 mg

4828 LDN 209929 dihydrochloride Potent and selective haspin kinase inhibitor 10 mg

50 mg



24 |

Other Protein Kinases – continued

Potent and Selective PERK Inhibitor

GsK 2606414 Cat. No. 5107

GSK.2606414.is.a.potent.and.selective.PERK.inhibitor.(IC50 = 0.4 nM).that.exhibits.>1000-fold.selectivity.for.PERK.over.HR1.and.PKR..The.compound.inhibits.thapsigargin-induced.PERK.phosphorylation.in.lung.carcinoma.cells.and.attenuates.subcutaneous.pancreatic.tumor.xenograft.growth.in.mice..GSK.2606414.is.also.orally.bioavailable.

(sold for research purposes only under agreement from GlaxosmithKline)

Potent and Selective PERK InhibitorGSK 2606414 (5107)

N

N

N

NH2

N

O

CF3


IKK (IκB kinase)

Inhibitors 4547 ACHP Selective IKKα and IKKβ inhibitor 10 mg

4857 Amlexanox Inhibitor of TBK1 and IKKε; antiallergic agent 10 mg

50 mg

2539 IKK 16 Selective inhibitor of IKK 10 mg

50 mg

2611 IMD 0354 Inhibitor of IKKβ 10 mg

50 mg

4899 ML 120B dihydrochloride IKK2-selective inhibitor 10 mg

50 mg

4238 PF 184 Potent and selective IKKβ inhibitor 10 mg

4569 PS 1145 dihydrochloride Selective IKK inhibitor; orally active 10 mg

50 mg

3318 SC 514 IKKβ inhibitor; attenuates NF-κB-induced gene expression 10 mg

50 mg

2559 TPCA-1 Potent, selective inhibitor of IKKβ 10 mg

Mps1 (Monopolar Spindle 1)

Inhibitors 3994 AZ 3146 Potent and selective Mps1 kinase inhibitor 10 mg

50 mg

5142 Mps1-IN-1 dihydrochloride Selective Mps1 kinase inhibitor 10 mg

4750 TC Mps1 12 Potent and selective Mps1 kinase inhibitor; orally active 10 mg

50 mg

PERK (PKR-like ER kinase)

Inhibitors 5107 GSK 2606414 Potent and selective PERK inhibitor; orally bioavailable 10 mg

50 mg

PLK (Polo-like Kinase)

Inhibitors 3116 Cyclapolin 9 Selective, ATP-competitive PLK1 inhibitor 10 mg

50 mg

2977 GW 843682X Selective inhibitor of PLK1 and PLK3 1 mg

10 mg

50 mg

4292 SBE 13 hydrochloride Potent and selective PLK1 inhibitor 10 mg

50 mg

4459 TC-S 7005 Potent and selective PLK2 inhibitor 10 mg

KINASES

www.tocris.com | 25

Atypical KinasesAtypical kinases are kinases that do not exhibit sequence similarity with conventional protein kinases, but are reported to have protein kinase activity. These include ATM and ATR kinases, mTOR, DNA-dependent protein kinase (DNA-PK) and eEF2 kinase (eEF2 K).

Featured Atypical Kinase Inhibitors

AZ 20 (5198)Potent and selective ATR kinase

inhibitor; antitumor

N

N

SO O

N

O

NH

NU 7441 (3712)Potent and selective DNA-PK inhibitor

O

O

N

OS

A 484954 (4483)eEF2K (CaM kinase III) inhibitor

N

NO

O

N

NH2

O

NH2

NO

O

Me

HOMe

O

Me

Me

OH

O

O

Me

Me

H

O

MeOMe

Me

MeO

H

OO

OH

O

HO

HO

Temsirolimus (5264)mTOR inhibitor; antitumor

Torin 1 (4247)Potent and selective mTOR inhibitor

N

NN

ON

N

O

CF3

Featured Atypical Kinase Inhibitors

ATM/ATR

Inhibitors 5198 AZ 20 Potent and selective ATR kinase inhibitor; antitumor 10 mg

50 mg

3544 KU 55933 Potent and selective ATM kinase inhibitor 10 mg

4176 KU 60019 Potent ATM kinase inhibitor 10 mg

50 mg

3190 Mirin MRN-ATM pathway inhibitor 10 mg

50 mg

DNA-PK (DNA-dependent Protein Kinase)

Inhibitors 3271 Compound 401 Selective DNA-PK and mTOR inhibitor 10 mg

50 mg

4840 KU 0060648 Dual DNA-PK and PI 3-K inhibitor 10 mg

50 mg

2828 NU 7026 Selective DNA-PK inhibitor 10 mg

50 mg

3712 NU 7441 Potent and selective DNA-PK inhibitor 10 mg

50 mg

eEF2K (CAM Kinase III)

Inhibitors 4483 A 484954 eEF2K (CaM kinase III) inhibitor 10 mg

50 mg

3439 NH 125 eEF2K (CaM kinase III) inhibitor 10 mg

50 mg



26 |

Atypical Kinases – continued

Licensing at TocrisTocris Bioscience has a long tradition of working with scientists to bring new discoveries out of the laboratory and into the commercial arena. We work in partnership with many scientists within both Universities and pharmaceutical companies to bring life science tools to the global research community.

Tocris policy has always been to never knowingly infringe third party intellectual property. It is our intention to remain a responsible and ethical supplier, and work with the scientific community.

Our ExpertiseOur licensing department has significant experience of drafting contracts and has successfully executed licenses with a multitude of licensors, including:

• Large pharmaceutical companies

• Start-up/Spin-out companies

• University Technology Transfer offices

• Individual researchers

Contact UsTo discuss licensing opportunities, please contact our licensing team at [email protected]


mTOR (Mammalian Target of Rapamycin)

Inhibitors 3725 KU 0063794 Selective mTOR inhibitor 10 mg

4079 Niclosamide mTORC1 signaling inhibitor; also inhibits STAT3 50 mg

4820 PF 04691502 Potent and selective dual mTOR/PI 3-K inhibitor 10 mg

50 mg

4823 PF 05212384 Potent and selective dual mTOR/PI 3-K inhibitor 10 mg

2930 PI 103 hydrochloride Inhibitor of mTOR, PI 3-kinase and DNA-PK 1 mg

10 mg

50 mg

4257 PP 242 Dual mTORC1/mTORC2 inhibitor 10 mg

50 mg

1292 Rapamycin mTOR inhibitor; immunosuppressant 1 mg

5264 Temsirolimus mTOR inhibitor; antitumor 10 mg

4247 Torin 1 Potent and selective mTOR inhibitor 10 mg

50 mg

4248 Torin 2 Potent and selective mTOR inhibitor 10 mg

50 mg

4282 WYE 687 dihydrochloride Potent and selective mTOR inhibitor 10 mg

50 mg

4893 XL 388 Potent and selective mTOR inhibitor; antitumor 10 mg

50 mg

KINASES

www.tocris.com | 27

Lipid KinasesLipid kinases have lipid molecules as their substrate, rather than proteins. These enzymes are particularly important for signal transduction. PI 3-kinase is a well-characterized member of this group; other members include diacylglycerol kinase and sphingosine kinase.

Potent and Selective PI 3-Kβ Inhibitor

aZd 6482 Cat. No. 4839AZD.6482.is.a.potent.and.selective.inhibitor.of.PI.3-kinase.β.(PI.3-Kβ).(IC50.values.are.0.69,.13.6,.47.8.and.136.nM.for.PI.3-Kβ,.PI.3-Kδ,.PI.3-Kγ.and.PI.3-Kα,.respectively)..The.compound.selectively.inhibits.PTEN-deficient.tumor.xenograft.growth.in vivo..AZD.6482.also.exhibits.antithrombotic.activity.

(sold with the permission of astraZeneca UK Ltd.)

Lipid Kinase section:Potent and Selective PI 3-Kβ Inhibitor

AZD 6482 (4839)

CO2HHN

N

N

O

N

O

CerK (Ceramide Kinase)

Inhibitors 3960 NVP 231 Potent, selective and reversible CerK inhibitor 10 mg

50 mg

DGK (Diacylglycerol Kinase)

Inhibitors 0484 Dioctanoylglycol DGK inhibitor 50 mg

2194 R 59-022 DGK inhibitor; increases PKC activity 10 mg

50 mg

PI 3-kinase

Activators 1983 740 Y-P Cell-permeable PI 3-kinase activator 1 mg

Inhibitors 3671 AS 252424 Selective inhibitor of PI 3-kinase γ 10 mg

3578 AS 605240 Potent and selective PI 3-kinase γ inhibitor 10 mg

50 mg

4839 AZD 6482 Potent and selective PI 3-Kβ inhibitor 10 mg

50 mg

3606 BAG 956 Dual PI 3-kinase and PDK1 inhibitor 10 mg

50 mg

4674 CZC 24832 Selective inhibitor of PI 3-kinase γ 10 mg

50 mg

4026 GSK 1059615 Potent PI 3-kinase inhibitor 10 mg

50 mg

4840 KU 0060648 Dual PI 3-kinase and DNA-PK inhibitor 10 mg

50 mg

1130 LY 294002 hydrochloride Selective PI 3-kinase inhibitor 5 mg

25 mg

2418 LY 303511 Negative control of LY 294002 (Cat. No. 1130) 5 mg

3977 3-Methyladenine Class III PI 3-kinase inhibitor; also inhibits autophagy 50 mg

4820 PF 04691502 Potent and selective dual PI 3-K/mTOR inhibitor 10 mg

50 mg

4823 PF 05212384 Potent and selective dual PI 3-K/mTOR inhibitor 10 mg

2814 PI 828 PI 3-kinase inhibitor; more potent than LY 294002 (Cat. No. 1130)

1 mg

10 mg

50 mg

3894 PP 121 PI 3-kinase family inhibitor; also inhibits tyrosine kinase receptors

10 mg

50 mg

1125 Quercetin Non-selective PI 3-kinase inhibitor 100 mg

4264 TG 100713 PI 3-kinase inhibitor 10 mg

50 mg

1232 Wortmannin Potent, irreversible inhibitor of PI 3-kinase; also PLK1 inhibitor

1 mg

5 mg

SphK (Sphingosine Kinase)

Inhibitors 4640 N,N-Dimethylsphingosine SphK inhibitor 10 mg

2097 SKI II Selective non-lipid inhibitor of SphK 10 mg

50 mg



28 |

Broad Spectrum Kinase Inhibitors Broad spectrum kinase inhibitors have a wide range of applications, particularly in high-throughput screening assays designed to discover selective inhibitors, where a standard inhibitor curve is required. Broad spectrum inhibitors are often both highly potent and cell permeable, offering a high degree of versatility.

Tocriscreen Kinase Inhibitor Toolbox includes 80 commercially available kinase inhibitors, often exclusive to Tocris. The Toolbox covers a wide range of kinase targets, including multiple inhibitors of commonly studied pathway mediators, such as EGFR, MAPK and AMPK cascades. Compounds are supplied pre-dissolved in DMSO for your convenience. For more information on our unique bioactive compound collections, please visit www.tocris.com/tocriscreen.

Key Format and Product details•. ..All.compounds.are.biologically.active.and.fully..

chemically.characterized

•. Many.compounds.are.unique.to.Tocris

•. A.selection.of.the.most.potent,.useful.kinase.inhibitors

•. Exceptional.purity,.supplied.in.a.convenient.format

•. 96-well.racks.with.Matrix.shortage.tubes.and.SepraSeal®.caps

tocriscreen™ Kinase inhibitor toolboxthe most important kinase targets all on one plate

www.tocris.com/tocriscreen

Product description size

tocriscreen Kinase inhibitor toolbox (3514)80.kinase.inhibitors.pre-dissolved.in.DMSO..(250.mL,.10.mM.solutions)

1.set

reference

Moujalled et al (2013) Kinase inhibitor screening identifies cyclin-dependent kinases and glycogen synthase kinase 3 as potential modulators of TDP-43 cytosolic accumulation during cell stress. PLoS One. 8 e67433

Broad Spectrum

Inhibitors 1227 Apigenin Protein kinase inhibitor 10 mg

50 mg

0542 H-7 dihydrochloride Protein kinase inhibitor 10 mg

50 mg

1520 Hypericin Inhibits tyrosine kinases 1 mg

1813 Indirubin-3’-oxime GSK-3β inhibitor; also inhibits other protein kinases 10 mg

50 mg

1745 5-Iodotubercidin Potent adenosine kinase inhibitor; also inhibits nucleoside transporters and a range of other kinases

1 mg

1683 K 252a Protein kinase inhibitor 200 µg

2992 PKC 412 Broad spectrum protein kinase inhibitor 1 mg

2002 Ro 31-8220 mesylate Protein kinase inhibitor 10 mg

1285 Staurosporine Non-selective protein kinase inhibitor 100 µg


KINASES

www.tocris.com | 29

PhosphatasesPhosphatases regulate the activity of kinases by catalyzing the removal of phosphate groups. This family of enzymes can be further subdivided by substrate specificity: Cdc25 phosphatases exhibit dual specificity, whilst protein Ser/Thr phosphatases and tyrosine phosphatases selectively remove phosphate groups from specific residues.

Potent and Selective Allosteric Inhibitor of Wip1 Phosphatase

GsK 2830371 Cat. No. 5140

GSK.2830371.is.a.potent.and.selective.allosteric.inhibitor.of.Wip1.phosphatase.(IC50 = 6 nM).that.exhibits.selectivity.for.Wip1.over.a.panel.of.21.other.phosphatases..The.compound.attenuates.proliferation.of.a.variety.of.lymphoid.cell.lines.and.inhibits.lymphoma.xenograft.growth.in vivo. GSK.2830371.is.also.orally.bioavailable.

(sold for research purposes only under agreement from GlaxosmithKline)

Phosphatases section

Potent and Selective Allosteric Inhibitor of Wip1 Phosphatase

GSK 2830371 (5140)

N

Cl

NH

S

HN

O ONH

Cdc25 Phosphatase

Inhibitors 1867 NSC 663284 Potent, selective Cdc25 phosphatase inhibitor 10 mg

1547 NSC 95397 Selective Cdc25 dual specificity phosphatase inhibitor 10 mg

50 mg

Inositol Phosphatase

Inhibitors 3718 AS 1949490 SH2 domain-containing inositol 5ʹ-phosphatase 2 (SHIP2) inhibitor

10 mg

50 mg

1420 D-myo-Inositol-1,3,4,5-tetrakisphosphate, octapotassium salt

Potent inhibitor of Ins(1,4,5)P3 5-phosphatase; metabolite of Cat. No. 1482

100 µg

0681 L-690,330 Inositol monophosphatase inhibitor 10 mg

50 mg

Other 0682 L-690,488 Cell permeable prodrug of the IMPase inhibitor L-690,330 (Cat. No. 0681)

5 mg

Protein Ser/Thr Phosphatase

Activators 0744 Ceramide Ser/Thr protein phosphatase activator 10 mg

50 mg

Inhibitors 4210 Ascomycin Calcineurin phosphatase inhibitor; analog of FK 506 (Cat. No. 3631)

1 mg

1336 Calyculin A Protein phosphatase 1 and 2A inhibitor 100 µg

1548 Cantharidin Protein phosphatase 1 and 2A inhibitor 50 mg

1101 Cyclosporin A Calcineurin inhibitor 100 mg

3631 FK 506 Potent calcineurin inhibitor; immunosuppressant 10 mg

1840 Fostriecin sodium salt Potent PP2A and PP4 inhibitor 50 µg

5140 GSK 2830371 Potent and selective allosteric inhibitor of Wip1 phosphatase 10 mg

50 mg

3930 NFAT Inhibitor Inhibitor of calcineurin-mediated NFAT activation 1 mg

1136 Okadaic acid Protein phosphatase 1 and 2A inhibitor 25 µg

2347 Salubrinal Selective inhibitor of eIF2α dephosphorylation 10 mg

2302 Sanguinarine chloride Inhibitor of protein phosphatase 2C (PP2C) 10 mg

50 mg

2305 Tautomycetin Selective PP1 inhibitor 50 µg

Protein Tyrosine Phosphatase

Inhibitors 3979 Alexidine dihydrochloride Selective inhibitor of PTPMT1 50 mg

2613 NSC 87877 Potent inhibitor of shp2 and shp1 PTP 50 mg

2754 TCS 401 Selective inhibitor of PTP1B 10 mg

3591 VO-OHpic Potent PTEN inhibitor 10 mg

50 mg



30 |

Kinase Inhibitor Classification Small molecule kinase inhibitors are valuable research tools for the study of many biological processes, including cell division, differentiation, proliferation and apoptosis. Kinase inhibitor classification is dependent on the binding-mode and region of interaction of the inhibitor with its target kinase.

Type I Kinase Inhibitors: Type 1 kinase inhibitors are ATP-competitive and typically bind to the ATP-binding pocket of the kinase in its phosphorylated, active conformation. The ATP-binding domain is highly conserved throughout the kinome, therefore type I kinase inhibitors often exhibit low selectivity.

Type II Kinase Inhibitors:Type II kinase inhibitors are non-ATP competitive and bind to the kinase in its inactive conformation. In the inactive state the activation loop is in a DFG-out conformation which exposes a hydrophobic (allosteric) binding pocket adjacent to the ATP binding site. Type II inhibitors interact with this allosteric binding pocket, as well as the ATP-binding domain. These inhibitors offer good selectivity.

Type III Kinase Inhibitors:Type III kinase inhibitors bind outside of the ATP binding pocket, solely to the allosteric binding pocket created by the DFG-out conformation. These inhibitors trap the kinase in an inactive conformation and offer high selectivity.

Type IV Kinase Inhibitors:Type IV kinase inhibitors are allosteric and bind to regions remote from the ATP binding pocket, stabilizing the kinase in an inactive conformation. As these allosteric regions exhibit significant diversity between kinases, these inhibitors are highly selective.

Type V Bivalent/Bisubstrate Inhibitors:Type V inhibitors consist of a ligand that targets the kinases ATP binding site and an allosteric ligand that binds to either the substrate binding site (bisubstrate) or another domain on the kinase (bivalent). The two ligands are coupled using a synthetic linker. These inhibitors offer greater selectivity over type I inhibitors and greater potency than type III and IV inhibitors.

Covalent Kinase Inhibitors:Covalent inhibitors form an irreversible covalent bond with the active site of the kinase, which blocks ATP binding and therefore irreversibly maintains the enzyme in an inactive conformation. These inhibitors are sometimes referred to as 'suicide' inhibitors.

References:Liu and Gray (2006) Rational design of inhibitors that bind to inactive kinase conformations. Nat.Chem.Biol 2 358.Lamba and Ghosh (2012) New directions in targeting protein kinases: focusing upon true allosteric and bivalent inhibitors. Curr.Pharm.Des. 18 2936.Fang et al (2013) Strategies for the selective regulation of kinases with allosteric modulators: exploiting exclusive structural features. ACS.Chem.Biol. 8 58.

Kinase Inhibitor Binding SchematicSchematic representing different types of kinase inhibitor-kinase interactions. Kinase inhibitors are shown as purple or red rectangles. Type I inhibitors bind to the ATP-binding pocket when the kinase is in its active conformation (DFG-in) and the activation loop is phosphorylated. Type II inhibitors bind to the kinases inactive conformation (DFG-out), interacting with the ATP binding domain and a hydrophobic binding pocket that is exposed due to the change in position of the DFG motif of the activation loop. Type III inhibitors bind the hydrophobic binding pocket, whilst type IV inhibitors bind to other allosteric sites on the kinase. Type V bivalent/bisubstrate inhibitors consist of two ligands attached by a synthetic linker. One ligand binds to the ATP binding pocket, whilst the other binds to an allosteric site on the kinase. Figure adapted from Foda and Seelinger (2014) Nat.Chem.Biol. 10 796.

Allosteric Binding Site

ATP Binding Pocket

DFG Binding Motif

Activation Loop

Type I Type II Type III + IV Type V

Hydrophobic Binding Pocket Synthetic LinkerInhibitor Inhibitor

P

KINASES

www.tocris.com | 31

Type I Inhibitors

Type II Inhibitors

CID 2011756 (4644)Pan PKD inhibitor; cell permeable

O

O

HN

Cl

N

O

NVP ADW 742 (5247)IGFR1 inhibitor; also inhibits c-Kit

NN

N

O

NH2

N

BIO (3194)Potent and selective GSK-3 inhibitor

XL 184 (5422)Potent VEGFR inhibitor; also inhibits other RTKs

N

O

O

O

NH

O

NH

OF

N

N

HN

MeO

HN

O

O

N

ON

O

HN

HN

O

OMe

OMe

OMe

N

S

ZM 447439 (2458)Aurora kinase B inhibitor

Ki 20227 (4481)c-Fms inhibitor

Type III + IV Inhibitors

PD 184352 (4237)Selective MEK inhibitor

F

F

HN

NH

O

Cl I

O S

OH

S

HO

GNF 5 (4908)Selective allosteric inhibitor of Bcr-Abl

IPA 3 (3622)Group I PAK inhibitor

Covalent Inhibitors

FIIN 1 hydrochloride (4002)Potent, irreversible FGFR inhibitor

N

NHN N

N

OHN

O

Cl

Cl

OMe

OMeHCl

N

Wortmannin (1232)Potent, irreversible inhibitor of PI 3-kinase;

also inhibits PLK1

O

O

O

Me

Me OO

Me O

MeO

O

NEtO

CN

HNHN

O

O

Cl

F

NMe2


NN

HNHNO

OCF3

HO

NH

NHO

NH

O

Br

Type I Inhibitors

Type II Inhibitors


O

O

HN

Cl

N

O


NN

N

O

NH2

N



N

O

O

O

NH

O

NH

OF

N

N

HN

MeO

HN

O

O

N

ON

O

HN

HN

O

OMe

OMe

OMe

N

S





F

F

HN

NH

O

Cl I

O S

OH

S

HO



Covalent Inhibitors


N

NHN N

N

OHN

O

Cl

Cl

OMe

OMeHCl

N


also inhibits PLK1

O

O

O

Me

Me OO

Me O

MeO

O

NEtO

CN

HNHN

O

O

Cl

F

NMe2


NN

HNHNO

OCF3

HO

NH

NHO

NH

O

Br

Type I Inhibitors

Type II Inhibitors


O

O

HN

Cl

N

O


NN

N

O

NH2

N



N

O

O

O

NH

O

NH

OF

N

N

HN

MeO

HN

O

O

N

ON

O

HN

HN

O

OMe

OMe

OMe

N

S





F

F

HN

NH

O

Cl I

O S

OH

S

HO



Covalent Inhibitors


N

NHN N

N

OHN

O

Cl

Cl

OMe

OMeHCl

N


also inhibits PLK1

O

O

O

Me

Me OO

Me O

MeO

O

NEtO

CN

HNHN

O

O

Cl

F

NMe2


NN

HNHNO

OCF3

HO

NH

NHO

NH

O

Br

Type I Inhibitors

Type II Inhibitors


O

O

HN

Cl

N

O


NN

N

O

NH2

N



N

O

O

O

NH

O

NH

OF

N

N

HN

MeO

HN

O

O

N

ON

O

HN

HN

O

OMe

OMe

OMe

N

S





F

F

HN

NH

O

Cl I

O S

OH

S

HO



Covalent Inhibitors


N

NHN N

N

OHN

O

Cl

Cl

OMe

OMeHCl

N


also inhibits PLK1

O

O

O

Me

Me OO

Me O

MeO

O

NEtO

CN

HNHN

O

O

Cl

F

NMe2


NN

HNHNO

OCF3

HO

NH

NHO

NH

O

Br

Type I Inhibitors

Type II Inhibitors


Covalent Inhibitors

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Documents

Kinases - Tocris Bioscience · Protein Kinases aGC Group ... 2546 PKI 14-22 amide, myristoylated Cell-permeable PKA inhibitor 1 mg PKC (Protein Kinase C) Activators 2383 Bryostatin