OSS_128167

OSS_128167 is a selective SIRT6 inhibitor with IC50s of 89, 1578 and 751 μM for SIRT6, SIRT1 and SIRT2, respectively.

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

Signaling Pathways >> Epigenetics >> Sirtuin

Research Areas >> Cancer

SIRT6:89 μM (IC50)

SIRT2:751 μM (IC50)

SIRT1:1578 μM (IC50)

OSS_128167 is a selective SIRT6 inhibitor with IC50s of 89, 1578 and 751 μM for SIRT6, SIRT1 and SIRT2, respectively. OSS_128167 inhibits SIRT6 in the micromolar range, but shows promising selectivity, since its IC50 value for SIRT6 is approximately 17 times lower compare to the IC50 for SIRT1 and 9 times lower compare to SIRT2[1]. OSS_128167 (200 μM) induces chemosensitization in primary multiple myeloma (MM) cells (NCI-H929), as well as in melphalan-resistant (LR-5) and doxorubicin-resistant (Dox40) MM cell lines[2].

TNF-a levels in supernatants from cells incubated for 18 h in the presence or absence of OSS_128167 (100 μM, final concentration) are measured by a commercially available ELISA kit according to the manufacturer’s instructions[1].

Glucose uptake is evaluated using a fluorescent D-glucose analog, 2-NBDG, in L6 cells incubated for 18 h in the presence or absence of OSS_128167 (100 μM, final concentration)[1].

[1]. Parenti MD, et al. Discovery of novel and selective SIRT6 inhibitors. J Med Chem. 2014 Jun 12;57(11):4796-804.

[2]. Cea M, et al. Evidence for a role of the histone deacetylase SIRT6 in DNA damage response of multiple myeloma cells. Blood. 2016 Mar 3;127(9):1138-50.

Selisistat (EX 527) | Nicotinamide | SRT1720 HCl | Sirtinol | 3-TYP | SRT 2104 | Fisetin | Thiomyristoyl | Cambinol | Tenovin-1 | CAY10602 | AK-7 | Inauhzin | Tenovin 6 Hydrochloride | Salermide