| 产品介绍 |
JIB-04 (NSC693627, E-isomer) is a potent, selective and cell permeable Jumonji histone demethylase inhibitor. Unlike the other known inhibitors, JIB-04 is not a competitive inhibitor of a-ketoglutarate. It inhibits the demethylase activity of Jumonji enzymes in vitro, with IC50 ~230 nM for JARID1A (KDM5A), ~440 nM for JMJD2A (KDM4A) and JMJD2B (KDM4B), ~340 nM for JMJD2E (KDM2E), and ~1 μM for JMJD3 (KDM6B) and JMJD2C (KDM4C). JIB-04 blocks Jumonji demethylase activity in cells and consequently inhibits cell growth, without affecting other a-ketoglutarate-dependent hydroxylases or histone-modifying enzymes, especially HDACs. JIB-04 alters transcriptional programs in cancer but not in normal cells, leading to cancer-specific cell death. Importantly, in vivo, JIB-04 lowers histone demethylase activity in tumors, reduces tumor burden and prolongs survival of mice in an aggressive breast cancer model.
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