1 research outputs found
EC144 Is a Potent Inhibitor of the Heat Shock Protein 90
Alkyne <b>40</b>, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7<i>H</i>-pyrrolo[2,3-<i>d</i>]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 <b>14</b> (BIIB021) that completed
phase II clinical trials. Alkyne <b>40</b> is more potent than <b>14</b> in an Hsp90α binding assay (IC<sub>50</sub> = 1.1
vs 5.1 nM) as well as in its ability to degrade Her-2 in MCF-7 cells
(EC<sub>50</sub> = 14 vs 38 nM). In a mouse model of gastric tumors
(N87), <b>40</b> stops tumor growth at 5 mg/kg and causes partial
tumor regressions at 10 mg/kg (po, qd×5). Under the same conditions, <b>14</b> stops tumor growth only at 120 mg/kg, and does not induce
partial regressions. Thus, alkyne <b>40</b> is approximately
20-fold more efficacious than <b>14</b> in mice