JIB-04 (199596-05-9) is a novel specific inhibitor of the Jumonji family of histone demethylases?in vitro, in cancer cells and in tumors?in vivo.?IC50?= 230, 340, 435, 445, 855 and 1100 nM for JARID1A, JMJD2E, JMJD2B, JMJD2A, JMJD3 and JMJD2C respectively.??Reduces tumor burden and prolongs life in a mouse model.1?Suppresses translation initiation and enhances mTOR inhibitor sensitivity.2?Inhibits the growth of temozolomide-resistant glioblastoma cells and crosses the blood brain barrier.3
JIB-04 is a specific inhibitor of Jumonji demethylases.
JIB-04 has been used in sulforhodamine B cell growth assay. It has also been used as a control to determine the inhibitory action of ML324 on KDM4A (histone lysine demethylase 4A).
JIB-04 is a selective inihibitor of Jumonji demethylases without inhibiting other α-ketoglutarate-dependent hydroxylases or histone-modifying enzymes including amine oxidase LSD1 (also known as KDM1A), which demethylates histone lysines. JIB-04 is a pan-inhibitor of Jumonji demethylases with JARID1A (KDM5A) being the most sensitive (IC50=230 nM) followed by JMJD2D (IC50=290 nM) and JMJD3 (KDM6B) and JMJD2C (KDM4C) more resistant (IC50 855 and 1100 nM, respectively). JIB-04 selectively inhibited viability of several human cancer cell lines with little toxicity towards normal cells, and also diminished tumor growth in two separate xenograft mouse models.
1) Wang?et al.?(2013),?A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth; Nature Commun., 4?2035
