SIRT6 Inhibitor

OSS_128167 is a potent selective sirtuin 6 (SIRT6) inhibitor with IC₅₀s of 89 μM, 1578 μM and 751 μM for SIRT6, SIRT1 and SIRT2, respectively. OSS_128167 has anti-HBV activity that inhibits HBV transcription and replication. OSS_128167 has anti-cancer, anti-inflammation and anti-viral effects.

SIRT6-IN-2 (Compound 5) is a selective and competitive SIRT6 inhibitor (IC₅₀: 34 μM). SIRT6-IN-2 increases acetylation of H3K9 and increases glucose uptake in cultured cells. SIRT6-IN-2 also reduces T cell proliferation. SIRT6-IN-2 has immunosuppressive and chemosensitizing effects.

SIRT6-IN-6 (compound 6d) is a potent and selective SIRT6 inhibitor with an IC₅₀ of 4.93 μM and a K_i of ~10 μM. SIRT6-IN-6 shows selectivity against other members of the HDAC family (SIRT1-3 and HDAC1-11). SIRT6-IN-6 significantly increases the level of glucose transporter GLUT-1, thereby reducing blood glucose in a mouse model of type 2 diabetes. SIRT6-IN-6 can be used for type 2 diabetes research.

SIRT6-IN-3 (compound 8a) is a selective inhibitor of SIRT6 (IC₅₀=7.49 μM). SIRT6-IN-3 inhibits pancreatic ductal adenocarcinoma (PDAC) cells proliferation and induces apoptosis. SIRT6-IN-3 increases the sensitivity of cancer cells to gemcitabine (HY-17026) via blocking the DNA damage repair pathway. SIRT6-IN-3 is used in pancreatic cancer research.

SIRT5 inhibitor 4 (compound 11) is a potent, selective SIRT5 inhibitor with IC₅₀ values of 26.4 and >400μM for SIRT5 and other SIRT subtype, respectively.

SIRT6-IN-5 (Compound 25) is a selective and safe SIRT6 inhibitor (IC₅₀ = 18.91 µM). SIRT6-IN-5 can enhance the anti proliferative effect of chemotherapy agents. SIRT6-IN-5 can be used in the research of cancer, such as breast cancer.

SIRT6-IN-4 (Compound 10d) is a selective inhibitor for SIRT6 with an IC₅₀ of 5.68 μM. SIRT6-IN-4 inhibits the proliferation of MCF-7 with an IC₅₀ of 8.30 μM. SIRT6-IN-4 arrests the cell cycle at G2/M phase, inhibits thecell migration and invasion of MCF-7, and induces apoptosis. SIRT6-IN-4 exhibits antitumor efficacy in mouse models.