A HDAC inhibitor
Pyroxamide is an inhibitor of histone deacetylase [1].
Histone deacetylases (HADC) are a series of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone and make the histones to wrap the DNA more tightly, which prevent transcription.
In murine erythroleukemia (MEL) cells, pyroxamide induced terminal differentiation and inhibited cells growth by apoptosis or cell cycle arrest. Also, pyroxamide increased the levels of acetylated histones H2A, H2B, H3 and H4. Pyroxamide inhibited HDAC1 activity with ID50 value of 100 nM [1]. In RD (embryonal) and RH30B cell lines, pyroxamide (1.25-20.0 μM) induced apoptosis and accumulation of acetylated histones. Also, pyroxamide induced the expression of p21/WAF1 protein and increased the sub-G1 fraction [2].
In mice bearing human CWR22 prostate cancer xenograft, pyroxamide (100 or 200 mg/kg) significantly suppressed the growth of the tumor and increased the expression of p21/WAF1 protein in a dose-dependent way [1].
参考文献:
[1].? Butler LM, Webb Y, Agus DB, et al. Inhibition of transformed cell growth and induction of cellular differentiation by pyroxamide, an inhibitor of histone deacetylase. Clin Cancer Res, 2001, 7(4): 962-970.
[2].? Kutko MC, Glick RD, Butler LM, et al. Histone deacetylase inhibitors induce growth suppression and cell death in human rhabdomyosarcoma in vitro. Clin Cancer Res, 2003, 9(15): 5749-5755.
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