12. Linear peptides (RGD >300 M; RGDS 26 M) Cyclic peptides Platelet aggregation test IC 50 =32 M IC 50 =72 nM IC 50 = 97 nM selective 1985- 1999 Searle, SK, Roche, Fujisawa, Rhone-Poulenc , Merck, Genentech, COR ther. IC 50 =26 nM selective IC 50 = 46 nM Selective Intravenous and oral administration
13.
14. Subset of a corporate library (Merck) containing amine and carboxylic acid functionalities at distance 10-20 Å IC 50 = 11 nM Selective N- -sulfonamide “ exosite” binding Platelet aggregation test IC 50 = 27 M Hit compound Hartman G.D. et al. J.Med. Chem. 1992, 35, 4640 IC 50 = 260 nM
15.
16. Magenta subunit Cyano subunit Xiao T. et al. Nature 2004, 32, 59
17. Table 1. Parenteral GPIIb-IIIa Antagonists Table 2. Clinical Status of Oral GPIIb-IIIa Antagonists
18.
19.
20. Tilley J.W. Et al JACS 1997, 119, 7589 Arkin M.R. et al. PNAS 2003, 100, 1603 Roche 24 Mimicking of R36 and E29 on IL-2R and bindind of E62 and K43 on IL-2 Biaryl alchene group in a deep groove
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