TOPIX

International Edition

NEWSLETTERTOPIX

Issue 3/2010

Cell Death, Cancer & Immunology

Fas Ligands 2

Apoptosis Detection Kits 3

Methionine Aminopeptidase 2 4

CDC25 4-5

Deubiquitinylating Enzymes 5

Compound Corner 6-7[NKT Cell Activators, Geldanamycin Analogs]

New Antibodies 8-9[BAFF; CEACAM; GPCRs; HSPs; LC3]

CD40/CD40L 10

Cytokine Kits 11

New Dkk-1 Products 12

www.enzolifesciences.com

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Fas LigandsFas (CD95; APO-1; TNFRSF6) is a member of the tumor necrosis factor (TNF) receptor superfamily and is an important media-tor of apoptotic cell death. Binding of the Fas ligand (FasL; CD95L; APO-1L; TNFSF6; CD178) to Fas induces the formation of the death-inducing signaling complex (DISC). The DISC consists of trimerized Fas, the death domain (DD) containing adapter molecule Fas-associated DD (FADD), procaspase-8a (FLICE; MACH1; MCH5), procaspase-8b (MACH2), procaspase-10 and the cellular FLIP (FADD-like interleukin-1β-converting enzyme inhibitory protein) proteins. The formation of the DISC results in the autoproteolytic cleavage of procaspase-8 and procaspase-10 and ultimately induces apoptosis. Fas-induced apoptosis can be effectively blocked at several stages by either FLICE-inhibitory protein (FLIP), by Bcl-2, or by the cytokine response modifi er A (CrmA). In addition to its role in apoptosis, Fas signaling plays a critical role in the immune system where it mediates killing of pathogen-infected cells and the death of obsolete and potentially dangerous lymphocytes.

FasL [CD95L; TNFSF6; CD178]

FasL (soluble) (human), (rec.)ALX-522-001-C010 10 µgALX-522-001-3010 SuperPack 3 x 10 µg Produced in HEK 293 cells. The extracellular domain of human FasL (APO-1L; CD95L; CD178) (aa 103-281) is fused at the N-terminus to a linker peptide (26 aa) and a FLAG®-tag. Glycosylation of rhsFasL is similar to that of natural human FasL. SPECIFICITY: Binds to human, mouse and rat Fas (CD95; APO-1). BIOLOGICAL ACTIVITY: Kills Jurkat cells at concentrations of >10ng/ml in the absence of a cross-linker. Cross-linking enhancer (see Set Prod. No. ALX-850-014) increases the activity of rhsFasL approx. 50-fold. ATTENTION: Results using sFasL may differ from those obtained with agonistic antibodies!LIT: Agonist antibody and Fas ligand mediate different sensitivity to death in the signaling pathways of Fas and cytoplasmic mutants: A.R. Thilenius, et al.; Eur. J. Immunol. 27, 1108 (1997) T cell costimulation by the TNF ligand BAFF: B. Huard, et al.; J. Immunol. 167, 6225 (2001) Loss of the BH3-only protein Bmf impairs B cell homeostasis and accelerates gamma irradiation-induced thymic lymphoma development: V. Labi, et al.; J. Exp. Med. 205, 641 (2008) For a comprehensive bibliography please visit our website.

FasL (soluble) (human), (rec.) setALX-850-014-KI02 1 Set SET CONTAINS:

10 µg of FasL (soluble) (human), (rec.) (Prod. No. ALX-522-001)•4 x 50 µg of Enhancer for Ligands (Prod. No. ALX-804-034) which in-•creases the biological activity (induction of apoptosis) by ~50-fold to a concentration range of 1-5ng/ml.

BIOLOGICAL ACTIVITY: Kills Fas-sensitive cells at concentrations of >1ng/ml in the presence of cross-linking enhancer. SPECIFIC ACTIVITY: ED50: 1ng/ml (A20 cells).LIT: Activation of Fas by FasL induces apoptosis by a mechanism that cannot be blocked by Bcl-2 or Bcl-x(L): D.C. Huang, et al.; PNAS 96, 14871 (1999) NF-κB signals induce the expression of c-FLIP: O. Micheau, et al.; Mol. Cell. Biol. 21, 5299 (2001) Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-depend-ent manner but can not functionally substitute caspase-8: M.R. Sprick, et al.; EMBO J. 21, 4520 (2002) The role of p53 and Fas in a model of acute murine graft-versus-host disease: S. Yada, et al.; J. Immunol. 174, 1291 (2005) Amplification of CD95 activation by caspase 8-induced en-dosomal acidification in rat hepatocytes: R. Reinehr, et al.; J. Biol. Chem. 283, 2211 (2008) For a comprehensive bibliography please visit our website.

The Standard Apoptosis Inducer!

Fas (human), mAb (APO-1-3)ALX-805-020-C100 Purified 100 µg CLONE: APO-1-3. ISOTYPE: Mouse IgG3. IMMUNOGEN: Human recombinant Fas (CD95; APO-1). SPECIFICITY: Recognizes human Fas. APPLICATION: FC, IP, WB.

Key Antibodies to FLIP

FLIP, mAb (Dave-2)ALX-804-127-C100 100 µg CLONE: Dave-2. ISOTYPE: Rat IgG2a. IMMUNOGEN: Recombinant human FLIP (aa 1-480). SPECIFICITY: Recognizes an epitope (aa 1-200) present in both short (FLIPS) and long (FLIPL) splice variants of human and mouse FLIP. APPLICATION: IP, WB.

FLIP (human), mAb (NF6)ALX-804-428-C050 50 µg ALX-804-428-C100 100 µg CLONE: NF6. ISOTYPE: Mouse IgG1. IMMUNOGEN: Recombinant human FLIP (aa 1-194). SPECIFICITY: Recognizes short (FLIPS) and long (FLIPL) splice variants of human FLIP. APPLICATION: WB.

Our Caspase-8 Gold Standards!

Caspase-8 (human), mAb (12F5)ALX-804-242-C100 100 µg CLONE: 12F5. ISOTYPE: Mouse IgG2b. IMMUNOGEN: Recombinant human cas-pase-8. SPECIFICITY: Recognizes human procaspase-8 and active human caspase-8. Detects procaspase-8 (p55/54), the intermediate cleavage prod-ucts (p43/41) and the p18 active subunit of caspase-8 by Western blot. Does not recognize mouse caspase-8. APPLICATION: IP, WB.

SuperFasLigand™ (soluble) (human), (rec.)ALX-522-020-C005 5 µg ALX-522-020-3005 SuperPack 3 x 5 µg Produced in HEK 293 cells. The extracellular domain of human FasL (APO-1L; CD95L; CD178) (aa 103-281) is fused at the N-terminus to a linker peptide (26 aa) and a FLAG®-tag. Glycosylation of rhsSuper-FasLigandTM is similar to natural human FasL. SPECIFICITY: Binds to human, mouse and rat Fas (CD95; APO-1). BIOLOGICAL ACTIVITY: Kills Fas-sensitive cells at concentrations of >1ng/ml. NOTE: Does not re-quire an enhancer. LIT: Fas ligand (CD95L) protects neurons against perforin-mediated T lymphocyte cytotoxicity: I. Medana, et al.; J. Immunol. 167, 674 (2001) Tumor-cell resistance to death receptor-induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax: H. LeBlanc, et al.; Nat. Med. 8, 274 (2002) Inhibition of metalloproteinase cleavage enhances the cyto-toxicity of Fas ligand: P.G. Knox, et al.; J. Immunol. 170, 677 (2003) In vitro engagement of CD3 and CD28 corrects T cell defects in chronic lymphocytic leukemia: M. Bonyhadi, et al.; J. Immunol. 174, 2366 (2005) For a comprehensive bibliography please visit our website.

Caspase-8 (mouse), mAb (1G12)ALX-804-447-C100 100 µg CLONE: 1G12. ISOTYPE: Rat IgG1. IMMUNOGEN: Recombinant mouse cas-pase-8 p18 subunit. SPECIFICITY: Recognizes the p18 subunit of mouse caspase-8. Detects bands of ~55kDa (full-length caspase-8) and ~18kDa (apoptosis-induced cleavage fragment) by Western blot. Does not cross-react with human caspase-8. APPLICATION: ELISA, FC, ICC, WB.

FIGURE: Detection of Fas ligand-induced cas-pase-8 processing and activation in human Jurkat cells.

METHOD: Jurkat cells were treated with Fas lig-and (100ng/ml).

Purified (PF) = Purified (Preservative free); FC = Flow Cytometry; ICC = Immunocytochemistry; IP = Immunoprecipitation; IHC = Immunohistochemistry (FS = Frozen Sections, PS = Paraffin Sections); WB = Western blot; BP = Blocking Peptide International Edition

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Apoptosis Detection KitsApoptosis Biomarker Assays for Clinical Diagnostics and Research The M30-Apoptosense® and M65® ELISA assays discrimi-nate between different modes of epithelial cell death by quantitative measurement of either the full-length cytok-eratin 18 (CK18) protein or one of the caspase-cleaved fragments of CK18 (ccCK18/CK18F).

The M30-Apoptosense® ELISA assay utilizes the M5 capture antibody and the M30 CytoDEATHTM antibody (ALX-804-590) to detect CK18 fragments containing neo-epitopes (NE) at positions 387-396, which are generated during the early stages of apoptosis by the action of cas-pases-3, -7 and -9. The M65® ELISA also detects cleaved fragments, however, it uses a different detection antibody from M30, namely M5, that does not distinguish between the full-length protein and its fragments. Thus, the M65® ELISA measures both caspase-cleavage (apoptosis) and cellular release of intact CK18 (necrosis).

Since both assays utilize the same recombinant CK18 protein fragment as a reference, the ratio of M65/M30 potentially becomes a readout, which provides additional information on the predominant mode of (tumor) cell death. These assays have been used in multiple pre-clinical and clinical research applications, but increasingly, are being used used as exploratory pharmacodynamic endpoints in clinical trials with apoptosis-modulating therapies.

Product Prod. No. Size

M30-Apoptosense® ELISA kit ALX-850-270-KI01ALX-850-270-5001

1 Kit5 x 1 Kit

M65® ELISA kit ALX-850-310-KI01 1 Kit

M30 CytoDEATHTM ELISA kit NEWALX-850-336-KI01 1 KitThe novel M30 CytoDEATH™ ELISA is designed as a high-throughput assay for functional screening and in vitro characterization of pro-apoptotic drugs using cell culture supernatants, and spheroid or tissue lysates (as it detects an intracellular physiological caspase substrate: CK18).

Cell Death Assays for Flow Cytometry or Microscopy

GFP-Certified™ Apoptosis/Necrosis detection kit ENZ-51002-25 25 AssaysENZ-51002-100 100 AssaysSpecifically designed for use with GFP-expressing cell lines and cells ex-pressing blue or cyan fluorescent proteins (BFPs, CFPs). The kit includes all the necessary reagents for determination of early and late stages of apop-tosis as well as necrosis. It is suitable for use with live or post-fixed cells in conjunction with probes, such as labeled antibodies, or other fluorescent conjugates displaying similar spectral properties as fluorescein or coumarin. Additionally, it provides quick and accurate results via flow cytometry and fluorescence/confocal microscopy.LIT: Cell Surface Externalization of Annexin A1 as a Failsafe Mechanism Preventing Inflammatory Responses during Secondary Necrosis: K.E. Blume, et al.; J. Immunol. 183, 8138 (2009), Sup-plemental Information

Nuclear-ID™ Green chromatin condensation detection kitENZ-51021-K200 200 AssaysProvides a rapid and convenient assay for one of the more prominent hall-marks of apoptosis, nuclear condensation. The kit contains a DNA interca-lating dye that brightly stains the condensed chromatin of apoptotic cells, but only dimly stains the normal chromatin of live cells. This staining pattern makes it possible to distinguish between healthy and apoptotic cell popula-tions by fluorescence microscopy or flow cytometry.

FIGURE: GFP-expressing cell line stained with GFP- Certified™ Apoptosis/Necrosis Detection SystemA: Viable cellsB: Early apoptotic cellsC: Late apoptotic cells D: Necrotic cellsD

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10µM β-LapachoneControl

FIGURE: Monitoring chromatin condensation arising from the application of an ap-optosis inducing agent. Jurkat cells (1x 106 cells/ml) were treated with the indicated drug for 4 hours. The flow cytometry study demonstrates the potential of using the assay for drug screening.

50µM BML-258


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Methionine Aminopeptidase 2 (MetAP2)M

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MetAP2 is a metalloenzyme that catalyzes removal of the N-terminal methionine from proteins, with the physiologically relevant metal thought to be either cobalt or manganese. Since it was identified as a target of the antiangiogenic natural product fumagillin (Prod. No. BML-CT100), it has been studied for its involvement in cancer, angiogenesis, inflammation, and rheumatoid arthritis. Because of differing substrate specificities and kinetics, it is not desirable to substitute bacterial methionine aminopeptidase for mammalian MetAP2.

FIGURE: Structural representation of human MetAP2 complexed with inhibitor A797859 (MMDB ID: 62187).

FumagillinBML-CT100-0001 1 mgBML-CT100-0005 5 mgInhibitor of angiogenesis and endothelial cell proliferation. Specific inhibi-tor of methionine aminopeptidase type 2 (MetAP2) by covalently modifying a conserved active-site histidine. Precursor to TNP-470. Exhibits antitu-mor activity in estrogen-induced pituitary adenoma. Antineoplastic. Anti-infective.LIT: The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2: N. Sin, et al.; PNAS 94, 6099 (1997) The anti-angiogenic agent fumagillin covalently modifies a conserved active-site histidine in the Escherichia coli methionine aminopeptidase: W.T. Lowther, et al.; PNAS 95, 12153 (1998) Molecular recognition of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2: E.C. Griffith, et al.; PNAS 95, 15183 (1998)

Met-AMC (fluorogenic substrate)BML-P236-0025 25 mgFluorogenic substrate for methionine aminopeptidase 2 (MetAP2) (kcat/Km=1.1 x 10 M-1min-1; Km=310 µM) or aminopeptidase N (Km=377µM). Ex.: 380nm, Em.: 460nm, although the following Ex/Em can also be used: 355,375/440,450. This substrate is useful for inhibitor screening and ki-netic analysis.

MetAP2 (human), (rec.) (GST-tag)BML-SE538-0010 10 µgRecombinant full-length (aa 1-478) methionine aminopeptidase 2 (MetAP2; p67eIF2; Eukaryotic initiation factor 2-associated protein), cloned from hu-man cDNA (NM_006838), expressed in insect cells, and purified using an N-terminal GST tag.

CDC25CDC25 protein tyrosine phosphatases dephosphorylate and activate cyclin dependent kinases, thus promoting cell division. All three of the genes encoding the CDC25 phosphatases are considered potential oncogenes and the enzymes are drug discovery targets.

CDC25 EnzymesActive, full-length CDC25s expressed in E. coli. Ideal for kinetic studies and inhibitor screening.


CDC25A (human), (rec.) BML-SE364-0050 50 µg

CDC25B (human), (rec.) BML-SE365-0050 50 µg

CDC25C (human), (rec.) BML-SE366-0050 50 µg

CDC25 Antibody

CDC25A, mAb (DCS-120)ADI-KAM-CC085-E 100 µgCLONE: DCS-120. ISOTYPE: Mouse IgG2. IMMUNOGEN: Recombinant human CDC25A protein. SPECIFICITY: Recognizes human, mouse and rat CDC25A. APPLICATION: IP, WB.

FIGURE: Western blot analysis of human HeLa cell lysate (1), mouse N1H/T3 cell lysate (2), and rat Rat-1 cell lysate (3), probed with KAM-CC085.

CDC25A


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CDC25 Inhibitors

ArtesunateBML-PR117-0010 10 mgBML-PR117-0050 50 mgArtesunate is a semisynthetic derivative of artemisinin. In addition to its well known antimalarial activity, it displays a profound cytotoxic action against fifty-five tumor cell lines. The molecular mode of action of artesunate in-volves down-regulation of CDC25A.LIT: Molecular modes of action of artesunate in tumor cell lines: T. Efferth, et al.; Mol. Pharmacol. 64, 382 (2003)

NSC-95397BML-EI309-0005 5 mgBML-EI309-0025 25 mgA potent and selective inhibitor of CDC25 phosphatase (Ki's for CDC25A, B and C are 32, 96 and 40 nM respectively). NSC-95397 inhibits the growth of several human tumor cell lines and blocks G2/M cell cycle transition. LIT: Identification of a potent and selective pharmacophore for Cdc25 dual specificity phosphatase inhibitors.: J.S. Lazo, et al.; Mol. Pharmacol. 61, 720 (2002)

Deubiquitinylating Enzymes (DUBs) and CancerMammals contain some 80-90 DUBs in fi ve different subfamilies, only a small number of which have been characterized with respect to the proteins that they interact with and deubiquitinylate. Several human DUBs are direct antagonists of oncogenic or tumor-suppressive E3 ligases and are increasingly being seen as potential targets in cancer therapies. Promising candidates include the nuclear DUBs, USP1, USP7 and USP28, which all control processes relevant to cancer. Specifi cally, USP1 has been shown to modulate DNA-repair checkpoints, whilst USP7 plays key roles in the p53 pathway (whereby it stabilizes both p53 and Hdm2) and USP28 is overexpressed in colon and breast tumors. Other DUBs have been shown to regulate the NF-κB signaling pathway, which is under the control of CYLD, a tumor-suppressor gene mutated in skin tumors. With reduced expression also found in tumors of the liver and kidney, it is possible that CYLD may have a more general role as a tumor suppressor. LIT: Targeting the ubiquitin system in cancer therapy: D. Hoeller and I. Dikic; Nature. 458, 438 (2009) Deubiquitylating enzymes and disease: S. Singhal, et al.; BMC Biochem. 9 Suppl. 1, S3 (2008) Protein partners of deubiquitinating enzymes: K.H. Ventii & K.D. Wilkinson; Biochem. J. 414, 161 (2008)

A Sensitive Fluorogenic Substrate

Ubiquitin-AMCBML-SE211-0025 25 µgA fluorogenic substrate for a wide range of DUBs, including ubiquitin C-terminal hydrolases (UCHs) and ubiquitin specific proteases (USPs). It is a useful reagent for the study of deubiquitinylating activity where detec-tion sensitivity or continuous monitoring of activity is essential.

A Potent and Specific Inhibitor

Ubiquitin aldehyde (rec.)BML-UW8450-0050 50 µgA potent, highly specific inhibitor of ubiquitin deconjugating enzymes, in-cluding all UCH and USP family members. Co-crystallization of ubiquitin aldehyde with specific deubiquitinylating enzymes has also been used to probe enzyme:substrate interactions.

Active Site-directed Probes

Ubiquitin vinyl sulfone, (HA-tag)BML-UW0155-0025 25 µgA useful reagent for the detection and identification of DUBs. HA-Ub-VS acts as a potent and irreversible inhibitor of DUBs through covalent modification of the active site, and as a specific probe for enzymes with DUB activity.


Ubiquitin vinyl methyl ester, (HA-tag) BML-UW0880-0025 25 µg

Chloroethyl ubiquitin, (HA-tag) BML-UW0885-0025 25 µg

Bromoethyl ubiquitin, (HA-tag) BML-UW0890-0025 25 µg

Also available:

FIGURE: DUB active site probe assay: Western blot showing reactions containing HAUbVS only (lane 1), HAUbVS + USP2cd (lane 2, Prod. No.BML-UW9850), and HAUbVS + GSTUCHL1 (lane 3, Prod. No. BML-UW9305),HAUbVSmodifiedproteinsdetected using HA-reactive polyclonal antibody (Sigma - H6908) at 1:2000 dilution.

HAUbVS-UCHL1

HAUbVS-USP2cd

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Compound Corner NKT Cell Activators

HIF-1a Modulators

a-GalCer was the first defined and most potent agonistic antigen of the natural killer T cell (NKT) T cell receptor (TCR). De-rivatives of a-GalCer stimulate the production of smaller amounts of IFN-g than a-GalCer, but induce equal or greater IL-4 secretion in mouse models.

a-GalCer Analog 7 NEWALX-306-032-C500 500 µg

a-GalCer Analog 8 NEWALX-306-033-C500 500 µgLIT: Synthesis and evaluation of 1,2,3-triazole containing analogues of the immunostimulant a-GalCer: T. Lee, et al.; J. Med. Chem. 50, 585 (2007)

KRN7000 [a-Galactosylceramide; a-GalCer]

BML-SL232-0100 100 µgBML-SL232-1000 1 mgKRN7000 is a synthetic analog of a-galactosylceramide and the marine natural product agelasphin. It is a specific ligand for human and mouse NKT cells and remains the best studied ligand of the lipid-binding MHC class I-like protein CD1d. It protects against LPS-induced shock and displays po-tent antitumor activity in various in vivo models. LIT: A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer: A. Ishikawa, et al.; Clin. Cancer Res. 11, 1910 (2005) Production and characterization of monoclonal antibodies against complexes of the NKT cell ligand alpha-galactosylceramide bound to mouse CD1d: K.O. Yu, et al.; J. Immunol. Methods 323, 11 (2007) For a comprehensive bibliography please visit our website.

Isoglobotrihexosylceramide[iGb3]

ALX-306-028-C100 100 µgALX-306-028-M001 1 mgLysosomal glycosphingolipid proposed to be the natural ligand of NKT cells. Stimulates natural killer T (NKT) cells similar to a-GalCer. For negative control compound see globotrihexosylceramide (Gb3) (Prod. No. ALX-306-030). LIT: Lysosomal glycosphingolipid recognition by NKT cells: D. Zhou, et al.; Science 306, 1786 (2004) Synthesis and biological evaluation of alpha-galactosylceramide (KRN7000) and isoglobotrihex-osylceramide (iGb3): C. Xia, et al.; Bioorg. Med. Chem. Lett. 16, 2195 (2006) Chemoenzymatic Syntheses of iGb3 and Gb3: Q. Yao, et al.; Org. Lett. 8, 911 (2006)

Dimethyl-bisphenol ABML-GR339-0010 10 mgBML-GR339-0050 50 mgPromotes degradation of HIF-1a.LIT: Bisphenol A, an environmental endocrine-disrupting chemical, inhibits hypoxic response via degradation of hypoxia-inducible factor 1alpha (HIF-1alpha): structural requirement of bisphenol A for degradation of HIF-1alpha: T. Kubo, et al.; BBRC 318, 1006 (2004)

DimethyloxaloylglycineBML-EI347-0010 10 mgBML-EI347-0050 50 mgDMOG is a cell permeable prolyl-4-hydroxylase inhibitor which upregulates HIF activity. HIF activation stimulates angiogenesis in several different models. DMOG also inhibits FIH (Factor Inhibiting HIF), an asparaginyl hydroxylase, which enhances the HIF response. It is active in vivo and attenuates myocardial injury in a rabbit ischemia reperfusion model (20mg/kg). Expected to be pro-angiogenic.LIT: Stimulation of HIF-1alpha, HIF-2alpha, and VEGF by prolyl 4-hydroxylase inhibition in human lung endothelial and epithelial cells: T.M. Asikainen, et al.; Free Radic. Biol. Med. 38, 1002 (2005) Activation of hypoxia-inducible factors in hyperoxia through prolyl 4-hydroxylase blockade in cells and explants of primate lung: T.M. Asikainen, et al.; PNAS 102, 10212 (2005)

a-GalCer Analog 7

a-GalCer Analog 8

O

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OHO

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O

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OH

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C14H29

C24H49

KRN7000 [a-GalCer]

Isoglobotrihexosylceramide

Dimethyl-bisphenol A

Dimethyloxaloylglycine


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Ionophore Antibiotics

Enniatins belong to a family of depsipeptides produced by several species of Fusarium. Enniatins have been shown to act as ionophores. Potential anticancer compounds.

LIT: Ionophore antibiotics produced by the fungus Fusarium orthoceras var. enniatum and other Fusaria: E. Gaumann, et al.; Experientia 3, 202 (1947) Enniatin exerts p53-dependent cytostatic and p53-independent cytotoxic activities against human cancer cells: R. Dornetshuber, et al.; Chem. Res. Toxicol. 20, 465 (2007) Enniatins A1, B and B1 from an endophytic strain of Fusarium tricinctum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation: W. Wätjen et al.; Mol. Nutr. Food Res. 53, 431 (2009) For a comprehensive bibliography please visit our website.

Enniatin A Enniatin A1 Enniatin B Enniatin B1

Latest Insight

Sivelestat sodium BML-PI157-0010 10 mgBML-PI157-0050 50 mgLIT: ONO-5046, a novel inhibitor of human neutrophil elastase: K. Kawabata, et al.; BBRC 177, 814 (1991)

Elasnin ALX-350-171-M001 1 mgALX-350-171-M005 5 mgLIT: Inhibition of human leukocyte elastase, porcine pancreatic elastase, and chymotrypsin by elasnin and other 4-hydroxy-2-pyrones: R.W. Spencer, et al.; J. Med. Chem. 28, 1828 (1985)

A recent publication by Houghton et al., demonstrates that neutrophil elastase acts through a unique intracellular mecha-nism to promote tumorigenesis. By examining neutrophil elastase localization, the authors found that the secreted enzyme is internalized by epithelial tumor cells, where it degrades the adapter IRS-1. This, in turn, frees PI 3-kinase to transduce pro-mitotic signals from the PDGF receptor. The study is of interest, not only for introducing a unique non-cell autonomous, intracellular mechanism for neutrophil elastase, but it also provides a potentially novel therapeutic ap-proach to lung cancer using anti-inflammatory drugs, in particular neutrophil elastase inhibitors. The authors show that the neutrophil elastase inhibitor sivelestat (BML-PI157), a drug approved in Japan, shows antitumor efficacy in mice.

LIT: Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth: A.M. Houghton et al.; Nat. Med. 16, 219 (2010)

O

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Product Isolated from Prod. No. Size

Enniatin A Fusarium sp. ALX-380-310-MC05 0.5 mg

Enniatin A1 Fusarium sp. ALX-380-311-M001 1 mg

Enniatin B Fusarium orthoceras var. enniatum. ALX-380-007-M001 1 mg

Enniatin B1 Fusarium sp. ALX-380-312-M001 1 mg

Geldanamycin Analogs

17-AAGBML-EI308-0001 1 mg17-AAG is a less toxic and more stable analog of geldanamycin (Prod. No. BML-EI280). Inhibitor of heat shock protein 90 (HSP90) that displays a 100-fold higher affinity for HSP90 derived from tumor cells compared to HSP90 from normal cells. 17-AAG inhibits Akt activation and expression in tu-mors and synergizes with a number of antitumor agents such as taxol, cisplatin, and UCN-014. 17-AAG causes the inactivation, destabilization and eventual degradation of HIF-1a. Inhibitor of telomerase activity. Inducer of apoptosis with an-titumor activity. Inducer of macroautophagy.LIT: A high-affinity conformation of Hsp90 confers tumour se-lectivity on Hsp90 inhibitors: A. Kamal, et al.; Nature 425, 407 (2003)

17-DMAGBML-EI337-0001 1 mgLess toxic, more potent synthetic derivative of geldanamycin (Prod. No. BML-EI280). Inhibitor of angiogenesis. Inhibitor of heat shock protein 90 (HSP90). Cytotoxic against multiple cancer cell types and inhibits angiogenesis. In-ducer of apoptosis with higher antitumor activity than 17-AAG (Prod. No. BML-EI308). 17-DMAG or geldanamycin reduces the uptake of chaperone medi-ated autophagy (CMA) substrates by iso-lated lysosomes.LIT: Enhanced tumor cell radiosensitivity and abroga-tion of G2 and S phase arrest by the Hsp90 inhibi-tor 17-(Dimethylaminoethylamino)-17-demethoxy-geldanamycin: E.E. Bull, et al.; Clin. Cancer Res. 10, 8077 (2004)


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New Antibodies CEACAMs CD5LCEA-related cell adhesion molecules (CEACAM) belong to the carcinoembryonic antigen (CEA) family. It consists of seven CEACAM (CEACAM1, CEACAM3 - CEACAM8) and 11 pregnancy-specifi c glycoprotein (PSG1 - PSG11) members which function as cell adhesion molecules, tumor suppressors, regulators of lymphocytes, activators of dendritic cells, and receptors of Neisseria species and other bacteria. Overexpression of CEA/CEACAM5 in tumors of epithelial origin is the basis of its wide-spread use as a tumor marker.

CEACAM5,6 (human), mAb (MUS)ALX-805-086-C100 100 µgCLONE: MUS. ISOTYPE: Mouse IgG1. IMMUNOGEN: Extracted human CEACAM5. SPECIFICITY: Recognizes human CEACAM5 and 6. Does not cross-react with human CEACAM1, 3, 4, 7 or 8. APPLICATION: FC, ELISA, IHC (FS), WB.

CEACAM8 (human), mAb (GM2H6)ALX-805-088-C100 100 µgCLONE: GM2H6. ISOTYPE: Mouse IgG1. IMMUNOGEN: Vector containing the cDNA of human CEACAM8. SPECIFICITY: Recognizes human CEACAM8. Does not cross-react with human CEACAM1, 3, 4, 5, 6, 7, or PSG1. APPLICATION: FC, ELISA.

CEACAM19 (human), mAb (HY-8H10)ALX-805-089-C100 100 µgCLONE: HY-8H10. ISOTYPE: Mouse IgG1. IMMUNOGEN: Vector containing the cDNA of human CEACAM19. SPECIFICITY: Recognizes human CEACAM19. Does not cross-react with human CEACAM1, 3, 4, 5, 6, 7, 8, 20, or 21. AP-PLICATION: FC, ELISA.

CEACAM20 (human), mAb (HT-12D8)ALX-805-090-C100 100 µgCLONE: HT-12D8. ISOTYPE: Mouse IgG1. IMMUNOGEN: Vector containing the cDNA of human CEACAM20. SPECIFICITY: Recognizes human CEACAM20. Does not cross-react with human CEACAM1, 3, 4, 5, 6, 7, 8, 19, or 21. AP-PLICATION: FC, ICC, ELISA.

PSG1 (human), mAb (BAP3)ALX-805-087-C100 100 µgCLONE: BAP3. ISOTYPE: Mouse IgG1. IMMUNOGEN: Extracted human PSG1. SPECIFICITY: Recognizes an epitope in the B2 domain of human PSG1. Does not cross-react with CEACAM1, 3, 5, 7 or 8. APPLICATION: FC.

Human CD5L (Spa; API6) inhibits tumor necrosis factor-a secretion by human monocytes stimulated with LPS or LTA. Binding of CD5L to conserved components of bacterial sur-faces and modulation of the monocyte response indicate that this molecule is an active constituent of the innate immune response of the host.

CD5L, mAb (9F3b)ALX-803-336-C100 100 µgCLONE: 9F3b. ISOTYPE: Mouse IgG1. IMMUNOGEN: Recombinant human CD5L. SPECIFICITY: Recognizes human and mouse CD5L. APPLICATION: IP, WB, ELISA.

CD5L (human), mAb (3B1a)ALX-803-337-C100 100 µgCLONE: 3B1a. ISOTYPE: Mouse IgG2. IMMUNOGEN: Recombinant human CD5L. SPECIFICITY: Recognizes human CD5L. APPLICATION: IP, WB, ELISA.

CD5L (mouse), mAb (1F1G5i)ALX-803-338-C100 100 µgCLONE: 1F1G5i. ISOTYPE: Rat IgG. IMMUNOGEN: Recombinant mouse CD5L. SPECIFICITY: Recognizes mouse CD5L. APPLICATION: IP, WB, ELISA.

FIGURE: Spectral confocal microscopy of CHO cells using CEACAM19 (human), mAb (HY-8H10) (Prod. No. ALX-805-089). CHO cells were transiently transfected with an expression vector encoding CEACAM19. Binding of CEACAM19 (human), mAb (HY-8H10) was visualized with a FITC-conjugated secondary antibody (green). Actin filaments are labeled with Alexa Fluor-555 Phalloidin (red). Cell nuclei are stained with DAPI (blue).

BAFF (BLyS; TALL1) is a cytokine expressed predomi-nantly by cells of the immune system such as neu-trophils, monocytes, macrophages, dendritic cells, follicular dendritic cells, activated T cells and some malignant B cells. BAFF is a master regulator of periph-eral B cell survival, and also acts in processes such as immunoglobulin isotype switch and B cell co-stimula-tion. Besides its major role in B cell biology, BAFF co-stimulates activated T cells. In humans, elevated levels of soluble BAFF have been detected in the serum of patients with various autoimmune diseases.

BAFF-R (human), mAb (HuBR9.1) ALX-804-883-C100 100 µg CLONE: HuBR9.1. ISOTYPE: Mouse IgG1. IMMUNOGEN: Cells transfected with human BAFF-R. SPECIFICITY: Recognizes human BAFF-R. APPLICATION: FC.

BAFF (human), mAb (blocking) (4.62)ALX-804-882-C100 100 µgCLONE: 4.62. ISOTYPE: Rat IgG2. IMMUNOGEN: HA-tagged human BAFF. SPECIFICITY: Recognizes human BAFF. APPLICATION: ELISA.

BAFF (human), mAb (2.81) ALX-804-884-C100 100 µg CLONE: 2.81. ISOTYPE: Rat IgG2. IMMUNOGEN: HA-tagged human BAFF. SPECIFICITY: Recognizes human BAFF. APPLICATION: ELISA.

New available:

BAFF (soluble) (human), matched pair detection setAG-46B-0001-001 1 Set


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LC3 Microtubule-associated protein 1 light chain 3 (LC3) belongs to the family of autophagy-defective gene-8 (Atg-8)-related proteins. It is expressed at suffi cient high levels and effi cient-ly recruited to autophagic vesicles in cells and tissues.

LC3B, mAb (2G6)ALX-803-081-C100 100 µgCLONE: 2G6. ISOTYPE: Mouse IgG1. IMMUNOGEN: Synthetic peptide corre-sponding to the N-terminus of LC3B. SPECIFICITY: Recognizes human, mouse, rat, monkey and hamster LC3B. Recognizes both forms of endogenous LC3B. Detects a band of ~18kDa (LC3B-I; cytoplasmic form) and a band of ~16kDa (LC3B-II; lipidated form) by Western blot. APPLICATION: IHC, WB.

LC3, mAb (5H3)ALX-803-082-C100 100 µgCLONE: 5H3. ISOTYPE: Mouse IgG1. IMMUNOGEN: Synthetic peptide corre-sponding to an internal sequence identical in LC3A, LC3B and LC3C. SPE-CIFICITY: Recognizes human LC3. Recognizes both forms of endogenous LC3. Detects a band of ~18kDa (LC3-I; cytoplasmic form) and a band of ~16kDa (LC3-II; lipidated form) by Western blot. APPLICATION: IHC, WB.

FIGURE: Endogenous LC3 punctae detected using LC3B, mAb (5F10) (Prod. No. ALX-803-080)

METHOD: The majority of LC3 was diffusely localized in unstimulated COS-7 cells, wheres punctated signals of LC3 increase after induction of autophagy by vinblastin stimulationfor2h.Cellswerefixedwithparaformaldehydefollowedbymethanoltreat-ment. Cells were permeabilized with 0.3% Triton X-100. (Image courtesy of I. Ciechom-ska and A. Tolkovsky, University of Cambridge, UK.)

CRISP3Cysteine-rich secretory protein 3 (CRISP3) belongs to the cysteine-rich secretory protein family. It is up-regulated in malignant prostatic epithelium and can therefore be used as a potential prostate cancer biomarker.

CRISP3 (human), mAb (LV-2A2) ALX-805-093-C100 100 µgCLONE: LV-2A2. ISOTYPE: Mouse IgG1. IMMUNOGEN: Vector containing the cDNA of human CRISP3. SPECIFICITY: Recognizes human CRISP3. APPLI-CATION: FC, ELISA.

New Antibody Sample PacksThe antibody sample packs include a set of related antibodies and positive control(s) for molecular chaperone, heat shock, oxidative stress, GPCR (G protein-coupled receptor), pain, obesity and cardiovascular research areas. They are designed to be cost effective and help you choose which of our many antibodies might work best for your particular sample type or application.

Product Application Prod. No. Size

HSP90, Ab sample pack WB ADI-PAK-010 8 x 25 µg

HSP90, Ab sample pack with protein standards WB ADI-PAK-011 10 x 25 µg

HSP70, Ab sample pack WB ADI-PAK-020 8 x 25 µg

HSP70, Ab sample pack with protein standards WB ADI-PAK-021 10 x 25 µg

HSP70, mAb sample pack WB ADI-PAK-040 8 x 25 µg

HSP70, mAb sample pack with protein standards WB ADI-PAK-041 10 x 25 µg

Heme oxygenase, Ab sample pack WB ADI-PAK-030 8 x 25 µg

Heme oxygenase, Ab sample pack with protein standards WB ADI-PAK-031 10 x 25 µg

GPCR pain, Ab sample pack Varies by product (Membrane ELISA, IHC, WB)

ADI-PAK-110 5 x 25 µg

GPCR obesity, Ab sample pack Varies by product (Membrane ELISA, IHC, WB)


GPCR cardio, Ab sample pack Varies by product (Membrane ELISA, IHC, WB)


unstimulated +vinblastine

LC3B, mAb (5F10)ALX-803-080-C100 100 µgCLONE: 5F10. ISOTYPE: Mouse IgG1. IMMUNOGEN: Synthetic peptide corre-sponding to the N-terminus of LC3B. SPECIFICITY: Recognizes human, mouse, rat, dog and hamster LC3B. Recognizes both forms of endogenous LC3B. Detects a band of ~18kDa (LC3B-I; cytoplasmic form) and a band of ~16kDa (LC3B-II; lipidated form) by Western blot. APPLICATION: IHC, WB.


10CD

40/C

D40

L [C

D15

4]

CD40/CD40L [CD154]CD40 is a costimulatory protein found on antigen presenting cells and is required for their activation. The binding of CD40L (CD154) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects. These include a variety of immune and inflammatory responses including stimulation of B cell proliferation, memory B cell development, T cell-dependent immunoglobulin class switching and induction of cytokine production.

CD40L (soluble) (human), (rec.)ALX-522-015-2010 2 x 10 µgALX-522-015-6010 SuperPack 6 x 10 µgProduced in E. coli. The extracellular domain of human CD40L (CD154) (aa 116-261) is fused at the N-terminus to a linker peptide (6 aa) and a FLAG®-tag. BIOLOGICAL ACTIVITY: Stimulates growth of B cells. The activity of rhsCD40L increases 1’000-fold (stimulation in the ng/ml range) in the presence of cross-linking enhancer (see Set Prod. No. ALX-850-064). For stimulation of mouse cells via CD40 use CD40L (soluble) (mouse), (rec.) (Prod. No. ALX-522-070 or ALX-850-075).LIT: Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with downregu-lation of its proapoptotic activity and loss of liver toxicity: P. Schneider, et al.; J. Exp. Med. 187, 12051 (1998) Synergy between CD40 ligation and IL-4 on fibroblast proliferation involves IL-4 receptor sig-naling: S.P. Atamas, et al.; J. Immunol. 168, 1139 (2002) Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells: N. Harada, et al.; BBRC 299, 488 (2002) HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection: S. Swingler, et al.; Nature 424, 213 (2003) For a comprehensive bibliography please visit our website.

CD40L (soluble) (human), (rec.) setALX-850-064-KI01 1 SetProduced in E. coli. The extracellular domain of human CD40L (CD154) (aa 116-261) is fused at the N-terminus to a linker peptide (6 aa) and a FLAG®-tag. APPLICATION: Can be used to activate human B cells and dendritic cells. Stimulates growth of human B cells. For stimulation of mouse cells via CD40 use CD40 (mouse), mAb (FGK45) (Prod. No. ALX-805-046).SET CONTAINS:

10 µg of CD40L, Soluble (human) (rec.) (Prod. No. ALX-522-015)•2 x 50 µg of Enhancer for Ligands (Prod. No. ALX-804-034), which in-•creases the biological activity of rhsCD40L at least 1’000-fold.

LIT: Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with down-regulation of its proapoptotic activity and loss of liver toxicity: P. Schneider, et al.; J. Exp. Med. 187, 1205 (1998) CD40 induces apoptosis in carcinoma cells through activation of cytotoxic ligands of the tumor necrosis factor superfamily: A.G. Eliopoulos, et al.; Mol. Cell. Biol. 20, 5503 (2000) TNF receptor-associated factor 6 is an essential mediator of CD40-activated proinflammatory pathways in monocytes and macrophages: L. Mukundan, et al.; J. Immunol. 174, 1018 (2005) Enhanced ac-tivation of human dendritic cells by inducible CD40 and Toll-like receptor-4 ligation: N. Lapteva, et al.; Cancer Res. 67, 10528 (2007) For a comprehensive bibliography please visit our website.

Technical NoteMegaCD40L™ is a high activity construct in which two trimeric CD40 ligands are artificially linked via the collagen domain of ACRP30/adiponectin. This construct very effectively simulates the natural membrane-assisted aggregation of CD40L. It provides a simple and equally potent alternative to mouse CD40L & enhancer combinations (Prod. No. ALX-850-075).

FIGURE: Graphical representation of MegaCD40L™ (soluble) (mouse), (rec.) (Prod. No. ALX-522-120).

FIGURE: MegaCD40L (soluble) (human), (rec.) (Prod. No. ALX-522-110) does not need an enhancer to induce B cells activation.

METHOD: PBL cells were incubated in 96-well plates (2x105 cells/well in 100µl RPMI supplemented with 10% FCS) for 24 hours at 37°C with the indicated concentration of MegaCD40L (soluble) (human), (rec.) or CD40L (soluble) (hu-man), (rec.) (Prod. No. ALX-522-015) in the presence and absence of 1µg/ml enhancer (Prod. No. ALX-804-034). Cells were washed with PBS and stained with 2µl each CD86-PE and CD19-FITC in 50µl FACS buffer (PBS, 5% fetal calf serum, 0.02% azide) for 20 min. at 4°C in the dark. After two washes in FACS buffer, samples were then analyzed by flow cytometry.

ACRP

CD40L

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1 37 12 41.

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ng/ml

MegaCD40L rhsCD40LrhsCD40L + enhancer

Related Products:


CD40 (human):Fc (human), (rec.) ALX-522-016-C050 50 µg

CD40 (human):COMP (human), (rec.) ALX-522-064-C010 10 µg

CD40L (soluble) (mouse), (rec.) ALX-522-070-2010 2 x 10 µg

CD40L (soluble) (mouse), (rec.) set ALX-850-075-KI01 1 Set

MegaCD40L™ (soluble) (mouse), (rec.) ALX-522-120-C010 10 µg

Fc (human):CD40L (soluble) (human), (rec.) ALX-522-076-C010 10 µg

Fc (human):CD40L (soluble) (mouse), (rec.) ALX-522-072-C010 10 µg

MegaCD40L™ (soluble) (human), (rec.)ALX-522-110-C010 10 µgProduced in CHO cells. The extracellular domain of human CD40L (CD154) (aa 116-261) is fused at the N-terminus to mouse ACRP30head-less (aa 18-111) and a FLAG®-tag. BIOLOGICAL ACTIVITY: Binds to human CD40. Induces B cell activation (as demonstrated by dose-dependent upregulation of CD86).LIT: Two adjacent trimeric Fas ligands are required for Fas signaling and formation of a death-inducing signaling complex: N. Holler, et al.; Mol. Cell. Biol. 23, 1428 (2003) Impaired CD40L signaling is a cause of defective IL-12 and TNF-alpha production in Sezary syndrome: circum-vention by hexameric soluble CD40L: L.E. French, et al.; Blood 105, 219 (2005)


11

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kine

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ogy

Cytokine Kits – Cancer and ImmunologyCytokine research has led to a better understanding of cancer biology. Inappropriately dividing cells activate immune responses first modulated by macrophages that secrete cytokines to stimulate dendritic cells to mature and present antigens to T cells. Ideally these T cells destroy the tumor. Tumor cells may avoid destruction by producing molecules that interfere with antigen presentation or maturation of dendritic cells. The inflammatory response may even aid in the growth of the tumor by promoting angiogenesis. Targeting these molecules for novel cancer therapeutics will aid in the treatment of many solid tumors and improve patient outcomes.

Product Application Sensitivity Prod. No. Size

IFN-g (human), EIA kit Culture supernatants, plasma, serum, and urine

2 pg/ml (range 25.6 - 1,000 pg/ml)

ADI-900-136 1 x 96 wells

IFN-g (mouse), EIA kit Culture supernatants, plasma, serum, and urine

10 pg/ml (range 37 - 3,000 pg/ml)

ADI-900-137 1 x 96 wells

IL-1β (human), EIA kit Plasma, serum, and urine of human origin 1 pg/ml (range 10.24 - 400 pg/ml)

ADI-900-130 1 x 96 wells

IL-1β (mouse), EIA kit Culture supernatants, plasma, and serum of mouse origin

3 pg/ml (range 15.6 - 1,000 pg/ml)

ADI-900-132 1 x 96 wells

IL-1β (rat), EIA kit Culture supernatants, plasma, and serum of rat origin

12 pg/ml (range 25.6 - 2,500 pg/ml)

ADI-900-131 1 x 96 wells

IL-2 (human), EIA kit Culture supernatants, plasma, and serum 6.6 pg/ml (range 7.81 - 500 pg/ml)

ADI-900-118A 1 x 96 wells

IL-2 (mouse), EIA kit Culture supernatants and serum 3.12 pg/ml (range 7.81 - 1,000 pg/ml)

ADI-900-042 1 x 96 wells

IL-4 (human), EIA kit Culture supernatants, plasma, serum, and urine

2 pg/ml (range 10.24 - 400 pg/ml)

ADI-900-145 1 x 96 wells

IL-4 (mouse), EIA kit Culture supernatants and serum 4.34 pg/ml (range 7.81 - 1,000 pg/ml)

ADI-900-043 1 x 96 wells

IL-6 (human), EIA kit Culture supernatants, plasma, serum, and urine

6.01 pg/ml (range 7.81 - 500 pg/ml)

ADI-900-033 1 x 96 wells

IL-6 (mouse), EIA kit Culture supernatants and serum 1.01 pg/ml (range 7.81-1,000 pg/ml)

ADI-900-045 1 x 96 wells

IL-8 (human), EIA kit Culture supernatants, plasma, and serum 0.64 pg/ml (range 7.8-1,000 pg/ml)

ADI-900-156 1 x 96 wells

IL-10 (human), EIA kit Culture supernatants, plasma, and serum 3.75 pg/ml (range 7.81 - 500 pg/ml)

ADI-900-036 1 x 96 wells

IL-10 (mouse), EIA kit Culture supernatants and serum 12 pg/ml (range 37 - 3,000 pg/ml)

ADI-900-148 1 x 96 wells

IL-33 (soluble) (human), detection set [for ELISA application]

Biological fluids (serum and cell culture supernatant)

5 pg/ml (range 0 - 500 pg/ml)

APO-54N-025-KI01 5 x 96 wells

Osteoprotegerin (human), ELISA kit

Serum, plasma and urine 2.8 pg/ml ALX-850-280-KI01 1 x 96 wells

Free Osteoprotegerin (human), detection set [for ELISA application]

Cell culture supernatant, plasma and serum

2 pg/ml (range 0 to 250 pg/ml)


Free Osteoprotegerin (human), ELISA kit

Biological fluids (serum, plasma and cell culture supernatant)

20 pg/ml (range 0.031 to 2 ng/ml)


TGF-β1 EIA kit Culture supernatants, plasma, and serum of human, mouse, rat, and cow origin

3.3 pg/ml (range 31.25 - 1000 pg/ml)

ADI-900-155 1 x 96 wells

TNF-a (human), EIA kit Culture supernatants, plasma, and serum 8.43 pg/ml (range 15.63 - 1,000 pg/ml)

ADI-900-099 1 x 96 wells

TNF-a (mouse), EIA kit Culture supernatants and serum 3.9 pg/ml (range 31.25 - 2,000 pg/ml)

ADI-900-047 1 x 96 wells

TNF-a (rat), EIA kit Culture supernatants 12.0 pg/ml (range 31.3 - 2000 pg/ml)

ADI-900-086A 1 x 96 wells

TNF-a, soluble (human), (rec.) set

ALX-850-060-KI01 1 Set

TNF-a, soluble (mouse), (rec.) set

ALX-850-061-KI01 1 Set


For Local Distributors please visit our Website.

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ZZ-T0310-1002

Wnt Signaling in CancerThe Wnt signaling pathway is a complex network of proteins including β-catenin, Wnt, frizzled and LRP receptors, dishevelled, GSK-3, APC, TCF, axin, and others. When Wnt binds to frizzled, dishevelled is recruited to the membrane and GSK-3 (which normally phophorylates β-catenin) is inhibited by this activation. This inhibition of GSK-3 permits β-catenin to become stabilized and releases it from the axin complex. β-Catenin then accumulates in the cytosol, translocates to the nucleus, and forms a complex with TCF to eventually regulate cellular proliferation (e.g. osteoblast and neuronal development), survival and apoptosis through the induction of target nuclear genes.

Several components (e.g. APC, axin, TCF) of the Wnt signaling pathway have been implicated in human tumors or experimental cancer models. In multiple myeloma, Dkk-1 is overexpressed and facilitates increased bone resorption and the appearance of osteolytic lesions characteristic of this type of cancer. Dkk-1 inhibits the Wnt pathway (see image) by binding to the LRP5/6 co-receptors, preventing interaction with Wnt, and facilitating the degradation of β-catenin through phosphorylation by GSK-3.

Dkk-1 (human), EIA kitADI-900-151 1 x 96 wells For the quantitative determination of human Dkk-1 in culture supernatants, plasma, and serum. SENSITIVITY: 0.98 pg/ml (range 7.81-500 pg/ml).

Dkk-1 (rat), EIA kitADI-900-171 1 x 96 wells For the quantitative determination of rat Dkk-1 in culture supernatants, plasma, and serum. SENSITIVITY: 26.1 pg/ml (range 39.1 - 1250 pg/ml).

Dkk-1 (mouse), EIA kit NEWADI-900-172 1 x 96 wells For the quantitative determination of mouse Dkk-1 in culture supernatants, plasma, and serum. SENSITIVITY: 116.7 pg/ml (range 125 - 4,000 pg/ml).

Dkk-1 (mouse), (rec.) NEWADI-KPR-CP100-D 50 µg ADI-KPR-CP100-F 200 µg Mature recombinant mouse Dkk-1 protein with N-terminal His-tag, expressed in E. coli.

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Technology

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