A SIRT1 inhibitor
JGB1741 is a small molecule SIRT1 inhibitor [1].
Sirtuins or Sir2 (silent information regulator 2)-related enzymes have originally been defined as a family of nicotinamide adenine dinucleotide-dependent enzymes which are involved in deacetylating lysine residue on multiple proteins. The sirtuins show highly conservation from archaebacteria to eukaryotes. The mammalian sirtuins SIRT1–SIRT7 have been implicated in a variety of cellular functions, such as gene silencing, over the control of the cell cycle and apoptosis, to energy homeostasis [2].
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].
参考文献:
[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.
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