Updated in 2/11/2011 9:44:46 AM      Viewed: 207 times      (Journal Article)
Acc. Chem. Res. 39 (11): 831–840 (2006)

Adventures in Drug Discovery: Potent Agents Based on Ligands for Cell-Surface Receptors

Bruce E Maryanoff
How does one go about discovering new drugs? This question is addressed by descriptions of drug discovery research in three project areas that pertain to antagonist ligands for cell-surface receptors. The molecular targets of interest are protease-activated receptor-1 (PAR-1), vasopressin receptors (V1a and V2 subtypes), and the fibrinogen receptor (GPIIb/IIIa). I present different approaches to the identification of high-affinity ligands for these receptors, en route to drug candidates. The PAR-1 project resulted in a pharmacological tool compound that facilitated in vivo proof-of-principle studies, whereas the vasopressin and fibrinogen receptor projects resulted in several preclinical development compounds, three of which advanced into human clinical trials.
DOI: 10.1021/ar040112l