In vitro activity: OSS_128167 (formerly SIRT6-IN-1) is a novel, potent and selective SIRT6 inhibitor with IC50 of 89, 1578 and 751 μM for SIRT6, SIRT1 and SIRT2, respectively. Although OSS_128167 inhibits SIRT6 in the micromolar range, it shows excellent selectivity, as its IC50 value for SIRT6 is approximately 17 times lower in comparison to the IC50 for SIRT1 and 9 times lower than SIRT2. OSS_128167 at 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 line.

Kinase Assay: TNFα 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 ELISA kit according to the manufacturer’s instructions

Cell Assay: 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).