1. Academic Validation
  2. EC144 is a potent inhibitor of the heat shock protein 90

EC144 is a potent inhibitor of the heat shock protein 90

  • J Med Chem. 2012 Sep 13;55(17):7786-95. doi: 10.1021/jm300810x.
Jiandong Shi 1 Ryan Van de Water Kevin Hong Ryan B Lamer Kenneth W Weichert Cristina M Sandoval Srinivas R Kasibhatla Marcus F Boehm Jianhua Chao Karen Lundgren Noelito Timple Rachel Lough Gerardo Ibanez Christina Boykin Francis J Burrows Marilyn R Kehry Theodore J Yun Erin K Harning Christine Ambrose Jeffrey Thompson Sarah A Bixler Anthone Dunah Pamela Snodgrass-Belt Joseph Arndt Istvan J Enyedy Ping Li Victor S Hong Andres McKenzie Marco A Biamonte
Affiliations

Affiliation

  • 1 Biogen Idec, 5200 Research Place, San Diego, California 92122, USA.
Abstract

Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-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 (IC(50) = 1.1 vs 5.1 nM) as well as in its ability to degrade Her-2 in MCF-7 cells (EC(50) = 14 vs 38 nM). In a mouse model of gastric tumors (N87), 40 stops tumor growth at 5 mg/kg and causes partial tumor regressions at 10 mg/kg (po, qd × 5). Under the same conditions, 14 stops tumor growth only at 120 mg/kg, and does not induce partial regressions. Thus, alkyne 40 is approximately 20-fold more efficacious than 14 in mice.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-13479
    99.58%, Hsp90 Inhibitor
    HSP