Coactivator-associated arginine methyltransferase 1 (CARM1) represents a valuable target for hormone-dependent tumors such as prostate and breast cancers. Here we report the enzyme and cellular characterization of the 1-benzyl-3,5-bis(3-bromo-4-hydroxybenzylidene)piperidin-4-one (7g) and its analogues 8a–l. Among them, 7g, 8e, and 8l displayed high and selective CARM1 inhibition, with lower or no activity against a panel of different PRMTs or HKMTs. In human LNCaP cells, 7g showed a significant dose-dependent reduction of the PSA promoter activity.

中文翻译：

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新型 3,5-双（溴羟基亚苄基）哌啶-4-酮作为辅激活剂相关的精氨酸甲基转移酶 1 抑制剂：酶选择性和细胞活性

辅激活因子相关的精氨酸甲基转移酶 1 (CARM1) 是激素依赖性肿瘤（如前列腺癌和乳腺癌）的重要靶标。在这里，我们报告了 1-benzyl-3,5-bis(3-bromo-4-hydroxybenzylidene)piperidin-4-one ( 7g ) 及其类似物8a – l的酶和细胞特征。其中，7g、8e和8l显示出高度和选择性的 CARM1 抑制，对一组不同的 PRMT 或 HKMT 具有较低的活性或没有活性。在人 LNCaP 细胞中，7g显示 PSA 启动子活性的显着剂量依赖性降低。