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Biologieal

Pyroxamide(NSC 696085) is a potent histone deacetylase inhibitor with an IC50 of 100 nM for HDAC-1. ^[1] In a study, administration of pyroxamide (100 or 200 mg/kg/day) to nude mice at doses that caused little evident toxicity significantly suppressed the growth of s.c. CWR22 prostate cancer xenografts. Despite the potent growth-inhibitory effects of pyroxamide in this tumor model, serum prostate-specific antigen levels in control versus pyroxamide-treated mice were not significantly different. It causes the accumulation of acetylated core histones in MEL cells cultured with the agent. Human CWR22 prostate tumor xenografts from mice treated with pyroxamide (100 or 200 mg/kg/day) showed increased levels of histone acetylation and increased expression of the cell cycle regulator p21/WAF1, compared with tumors from vehicle-treated control animals. ^[2]

Reference

[1] Remiszewski SW. Curr Opin Drug Discov Devel. 2002 Jul;5(4):487-99.