JGB1741

JGB1741 (ILS-JGB-1741) is a potent and specific SIRT1 activity inhibitor with an IC50 of ∼15 μM. JGB1741 is a weak SIRT2 and SIRT3 inhibitor with an all IC50>100 μM. JGB1741 increases the acetylated p53 levels leading to p53-mediated apoptosis with modulation of Bax/Bcl2 ratio, cytochrome c release and PARP cleavage. JGB1741 has the potential for breast cancer research[1].

Signaling Pathways >> Epigenetics >> Sirtuin

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Sirtuin

SIRT1:∼15 μM (IC50)

SIRT2:>100 μM (IC50)

SIRT3:>100 μM (IC50)

JGB1741 (ILS-JGB-1741; 1-10000 nM; 24 h) inhibits MDA-MB 231 cell proliferation[1]. JGB1741 (0.01-1 μM; 24 h) induces apoptosis of MDA-MB 231 cells[1]. JGB1741 (0.01-1 μM; 24 h) shows a cell cycle arrest at G1 phase with more and more cells entering into sub G0/G1 phase[1]. JGB1741 (0.01-1 μM; 24 h) shows an increase in the global acetylation of H3K9, p53 expression and acetylated p53K382 levels[1]. Cell Proliferation Assay[1] Cell Line: K562, HepG2 and MDA-MB 231 cell lines Concentration: 1, 10, 50, 100, 500, 1000, 10000 nM Incubation Time: 24 hours Result: Inhibited MDA-MB 231 cell proliferation more potently with an IC50 of 0.5 μM than K562 and HepG2 cell proliferation (IC50>1 μM). Apoptosis Analysis[1] Cell Line: MDA-MB 231 cells Concentration: 0.01, 0.1, 0.5, 1 μM Incubation Time: Result: Showed an increase in the percent apoptotic cells in a dose-dependent fashion with ∼70% apoptosis at 1 μM concentration. Cell Cycle Analysis[1] Cell Line: MDA-MB 231 cells Concentration: 0.01, 0.1, 0.5, 1 μM Incubation Time: Result: Showed a cell cycle arrest at G1 phase with more and more cells entering into sub G0/G1 phase, the apoptotic phase, in a dose-dependent fashion. Western Blot Analysis[1] Cell Line: MDA-MB 231 cells Concentration: 0.01, 0.1, 0.5, 1 μM Incubation Time: Result: Caused a dose-dependent increase in the global acetylation of H3K9. Showed an increase in both p53 expression and acetylated p53K382 levels.

[1]. Arunasree M Kalle, et al. Inhibition of SIRT1 by a small molecule induces apoptosis in breast cancer cells. Biochem Biophys Res Commun. 2010 Oct 8;401(1):13-9.