Kinase experiment:

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].

Cell experiment:

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].

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

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].

[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.