2. Academic Validation
  3. 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.
PMID: 22938030 DOI: 10.1021/jm300810x
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