OSS_128167,IC-0128590

OSS_128167 is a potent selective sirtuin 6 (SIRT6) inhibitor with IC50s of 89 ¦ÌM, 1578 ¦ÌM and 751 ¦ÌM 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[1][2].

Western Blot Analysis[1]

Cell Line: BxPC3 cells

Concentration: 100 ¦ÌM

Incubation Time: 0 hours, 2 hours, 6 hours, 18 hours, 24 hours

Result: Increased H3K9 acetylation.

RT-PCR[2]

Cell Line: HepG2.2.15 and HepG2-sodium taurocholate cotransporting polypeptide (NTCP) cells

Concentration: 100 ¦ÌM

Incubation Time: 96 hours

Result: Significantly decreased HBV core DNA and 3.5-Kb RNA levels.

Animal Model: Male HBV transgenic mice (6-8-week-old)[2]

Dosage: 50 mg/kg

Administration: Intraperitoneal injection; every 4 days; for 12 days

Result: The level of HBV DNA and 3.5-Kb RNA were markedly suppressed in HBV transgenic mice.

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

[2]. Jiang H, et al. SIRT6 Inhibitor, OSS_128167 Restricts Hepatitis B Virus Transcription and Replication Through Targeting Transcription Factor Peroxisome Proliferator-Activated Receptors ¦Á. Front Pharmacol. 2019 Oct 25;10:1270.  

[3]. 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.