EC144 is a potent inhibitor of the heat shock protein 90

J Shi, R Van de Water, K Hong, RB Lamer…

Index: Shi, Jiandong; Van De Water, Ryan; Hong, Kevin; Lamer, Ryan B.; Weichert, Kenneth W.; Sandoval, Cristina M.; Kasibhatla, Srinivas R.; Boehm, Marcus F.; Chao, Jianhua; Lundgren, Karen; Timple, Noelito; Lough, Rachel; Ibanez, Gerardo; Boykin, Christina; Burrows, Francis J.; Kehry, Marilyn R.; Yun, Theodore J.; Harning, Erin K.; Ambrose, Christine; Thompson, Jeffrey; Bixler, Sarah A.; Dunah, Anthone; Snodgrass-Belt, Pamela; Arndt, Joseph; Enyedy, Istvan J.; Li, Ping; Hong, Victor S.; McKenzie, Andres; Biamonte, Marco A. Journal of Medicinal Chemistry, 2012 , vol. 55, # 17 p. 7786 - 7795

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Citation Number: 18

Abstract

Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3, 5-dimethylpyridin-2-yl) methyl)-7 H-pyrrolo [2, 3-d] pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that completed phase II clinical trials. Alkyne 40 is more potent than 14 in an Hsp90α binding assay (IC50= 1.1 vs 5.1 nM) as well as in its ...