IBC’s 10th Annual World CongressDRUG DISCOVERY TECHNOLOGY

AND DEVELOPMENT 2005Boston, MA, USAAugust 8–11, 2005

Alexander Scriabine

Yale University School of Medicine, New Haven, CT, USA

Keywords: Calcium assays — DG041 — High throughput screening.

The 10th Annual Congress of International Business Communications (IBC) entitled

Drug Discovery Technology & Development was held at the Boston Convention & Exhi-

bition Center from August 8–11. The congress consisted of 28 sessions with 3 to 8 pre-

sentations each, two keynote addresses and 155 posters. The exhibit hall had over 300

exhibits, mostly from contract service organizations and laboratory equipment manufac-

turers, but also from major pharmaceutical and start-up companies. Over 4000 attendees

were registered for the congress. The presentations and posters discussed largely tech-

niques used in drug research, including chemical synthesis, high throughput screening and

lead optimization. This report deals with selected reports on new technology useful in the

search for new cardiovascular drugs as well as with the discovery of novel drugs affecting

the cardiovascular system.

J. Dzubay (Invitrogen, Carlsbad, CA, USA) developed a new calcium assay for high

throughput drug screening, Fluo-4NW. Unlike the older assay (Fluo-4AM) the new assay

does not require removal of the dye loading solution and leads to more intense fluores-

cence. The assay was tested with CHO, HEK293 and non-adherent Jurkat cells.

A. Gao (Corning, Inc., Corning, NY, USA) optimized and miniaturized a calcium mo-

bilization assay that is commonly used to screen ligands of G-protein-coupled receptors.

The required volume of drug solution was reduced from 100 to 25 ìL for 384 well

microplates.

M. Karlsson (Cellectricon AB, Göteborg, Sweden) described new Dynaflow system,

an automatic patch-clamp technique, for discovery of drugs affecting ion channels. It uti-

lizes microfluidic chip technology that allows rapid sequential drug applications to patch-

clamped cells. The system can be used for high throughput screening as well as for safety

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Cardiovascular Drug ReviewsVol. 23, No. 3, pp. 278–279© 2005 Neva Press, Branford, Connecticut

Address correspondence and reprint requests to: A. Scriabine, M.D., Department of Pharmacology, Yale Uni-

versity School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA

pharmacology testing. Dynaflow chips are now available with 8, 16, or 48 channel

configurations.

Haiching Ma (Reaction Biology Corporation, Malvern, PA, USA) developed an ultra

high throughput functional screening microarray system, that requires only 1 nL of drug

solution. The system is ideal for assays of enzyme inhibitors and allows rapid IC50 deter-

minations for the test compounds.

Mark Gurney (deCode Genetics, Inc., Reykjavik, Iceland) discussed DG041, a novel

and selective antagonist at EP3 receptor for PgE2 for treatment of peripheral vascular

disease. Pharmacological, toxicological and Phase I clinical evaluation of this drug has

been completed. DeCode Genetics is also developing DG031, a leukotriene B4 inhibitor

licensed from Bayer AG. DG031 is in Phase III clinical evaluation for prevention of heart

attacks. In collaboration with Roche deCode Genetics is developing PDE4 inhibitors for

the treatment of vascular diseases, including stroke.

Richard Sportsman (Molecular Devices Corporation, Sunnyvale, CA, USA) de-

scribed a novel fluorescent assay for quantification of uptake of non-esterefied long-chain

fatty acids. The assay allows real-time measurements of fatty acid transport kinetics using

fluorescent plate reader. Hormone-induced changes in long chain fatty acid uptake have

been demonstrated in 3T3-L1 cells. This technique is expected to be useful in the search

for new anti-obesity drugs.

Eva Estebanez-Perpina (University of California at San Francisco, San Francisco,

CA, USA) developed a high throughput screening method for inhibitors of binding of thy-

roid hormone receptors with coregulator proteins. Inhibition of this protein-protein

binding is expected to influence gene transcription in the presence of thyroid hormone.

Small molecule inhibitors of this binding with Ki of 3000 nM were discovered.

Alex Kiselyov (ChemDiv, Inc., San Diego, CA, USA) identified three novel chemical

series of dual inhibitors of endothelin (ETA) and angiotensin (AT1) receptors with Kis of

less than 250 nM. Lead candidates with high specificity for the two types of receptors

were selected for further studies. The in vitro pharmacokinetic studies were favorable.

In vivo antihypertensive efficacy studies are in progress.

Daniel Lagasse (Archemix, Inc, Cambridge, MA, USA) described discovery and pre-

clinical evaluation of von Willebrand factor antagonist (DNA aptamer) for the treatment

of acute coronary syndrome. At 100 nM this antagonist inhibits botrocetin-induced aggre-

gation of human platelets in platelet rich plasma and shear stress-induced aggregation in

citrated whole blood. It was shown to inhibit platelet function in vivo in cynomolgus

monkeys.

Cardiovascular Drug Reviews, Vol. 23, No. 3, 2005

DRUG DISCOVERY TECHNOLOGY AND DEVELOPMENT 2005 279