Description
JIB-04 (199596-05-9) is a novel specific inhibitor of the Jumonji family of histone demethylasesin vitro, in cancer cells and in tumorsin 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.1Suppresses translation initiation and enhances mTOR inhibitor sensitivity.2Inhibits the growth of temozolomide-resistant glioblastoma cells and crosses the blood brain barrier.3
Uses
JIB-04 is a specific inhibitor of Jumonji demethylases.
Uses
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).
Biochem/physiol Actions
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.
in vivo
JIB-04 results in a significant reduction in cancer-induced death rates in mice, prolonging survival[1]. JIB-04 (60, 40 and 20 mg/kg, i.p.) reaches bioactive concentration in the brain of the mice. The orthotopic GB xenograft model shows a trend toward longer survival in JIB-04-treated mice with an Hazard Ratio of 0.5[2].
References
[1] LEI WANG. A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth.[J]. Nature Communications, 2013: 2035. DOI:
10.1038/ncomms3035
