Angiotensin II human

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Epigenetics-

JIB-04 ??? Jumonji ????????????????????? (Jumonji histone demethylase) ??????????????????????????? JARID1A???JMJD2E???JMJD3???JMJD2A???JMJD2B???JMJD2C ??? JMJD2D ???????????????IC50???????????? 230???340???855???445???435???1100 ??? 290 nM???

Histone Demethylase

相关产品

GSK-J4-GSK2879552-SP2509-Tranylcypromine hemisulfate-ORY-1001-ML324-IOX1-CPI-455-Daminozide-KDM5-IN-1-CBB1007-DDP-38003 dihydrochloride-KDM5A-IN-1-NCGC00244536-CBB1003-

生物活性

Description

JIB-04 is a pan-selectiveJumonji histone demethylaseinihibitor withIC50s of 230, 340, 855, 445, 435, 1100, and 290 nM for JARID1A, JMJD2E, JMJD3, JMJD2A, JMJD2B, JMJD2C, and JMJD2D, respectively.

IC50& Target

IC50: 230 nM (JARID1A), 445 nM (JMJD2A), 435 nM (JMJD2B), 1100 nM (JMJD2C), 290 nM (JMJD2D), 340 nM (JMJD2E), 855 nM (JMJD3)[1]

In Vitro

JIB-04 is consistently selective for cancer vs. normal cells, demonstrated by the higher sensitivity of lung and prostate cancer lines (with IC50??as low as 10 nM) compared to HBECs and PrSCs/PrECs. JIB-04 inhibits cellular Jumonji demethylase activity, and Jumonji levels affect JIB-04 action in cells[1]. JIB-04 significantly inhibits the proliferation of GB cell lines and stem-enriched cultures. JIB-04 exerts its maximal inhibitory activity against KDM5A, and modulates the expression of genes involved in the control of cancer cell growth and leads to hypermethylation of H3K4. Furthermore, JIB-04 (2500 nM) activates the autophagy and apoptotic pathways and inactivates PI3K. JIB-04 also cooperates with TMZ in killing GB cells[2].

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].Wang L, et al. A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth. Nat Commun, 2013. 4: p. 2035.

[2].Banelli B, et al. Small molecules targeting histone demethylase genes (KDMs) inhibit growth of temozolomide-resistant glioblastoma cells. Oncotarget. 2017 Apr 4.