Description
The sirtuins (SIRTs) are a family of NAD+-dependent histone deacetylases involved in gene regulation that is relevant to longevity, cancer, gene regulation, energy homeostasis, and apoptosis. JGB1741 is a small molecule inhibitor of SIRT1 with an IC50 value of 15 μM in a cell-free assay. It shows relatively weak inhibition for SIRT2 and SIRT3 with IC50 values greater than 100 μM. JGB1741 inhibits metastatic breast cancer MDA-MB 231 cell proliferation with an IC50 value of 512 nM in a cell-based assay and dose-dependently increases p53 acetylation and p53-mediated apoptosis in these cells.
Uses
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].
in vitro
jgb1741 potently inhibited the proliferation of human metastatic breast cancer cells, mda-mb 231. jgb1741 showed antitumor effects on three different cancer cell lines, k562, hepg2 and mda-mb 231 with an ic50 of 1, 10 and 0.5 μm, respectively. jgb1741-induced apoptosis has been associated with increase in cytochrome c release, modulation in bax/bcl2 ratio and cleavage of parp [1].
IC 50
SIRT1: ～15 μM (IC50); SIRT2: >100 μM (IC50); SIRT3: >100 μM (IC50)
References
[1] kalle a m, mallika a, badiger j, et al. inhibition of sirt1 by a small molecule induces apoptosis in breast cancer cells[j]. biochemical and biophysical research communications, 2010, 401(1): 13-19.
[2] yamamoto h, schoonjans k, auwerx j. sirtuin functions in health and disease[j]. molecular endocrinology, 2007, 21(8): 1745-1755.
