Zn
2+
-chelating motif-tethered fatty acids as histone deacetylase (HDAC) inhibitors. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)-benzamide (HTPB), displayed nM potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at sub-μM concentrations showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21
WAF/CIP1
expression, hallmark features associated with intracellular HDAC inhibition.
Zn2+螯合基固定的
脂肪酸作为组蛋白
去乙酰化酶(H
DAC)
抑制剂。一种羟酰胺基固定的苯
丁酸化合物,N-羟基-4-(4-苯丁酰
氨基)-苯甲酰胺(HTPB),在抑制H
DAC活性方面表现出纳摩尔级别的效力。将几种癌
细胞系暴露于亚微米浓度的HTPB中,显示出细胞增殖减少,伴随着组蛋白高乙酰化和升高的p21WAF/
CIP1表达,这是与细胞内H
DAC抑制相关的标志性特征。