Sirtuin 6 (SIRT6) is a NAD+-dependent deacetylase that regulates DNA repair, telomere maintenance, glucose and lipid metabolism, inflammation, and cancer. OSS_128167 is a selective SIRT6 inhibitor with IC50 values of 89 ± 5μM, 1578 ± 47μM, and 751 ± 23μM for SIRT6, SIRT1, and SIRT2, respectively[4]. OSS_128167 inhibited hepatitis B virus (HBV) transcription and replication in vitro at a concentration of 100μM. In HepG2.2.15 and HBV-infected HepG2-sodium taurocholate cotransporting polypeptide cells, the promotion of SIRT6 overexpression on HBV transcription and replication was blocked by OSS_128167 at 100μM. Administration of HBV transgenic mice with 50mg/kg OSS_128167 resulted in a significant reduction of HBV DNA in serum, as well as serum hepatitis B surface antigen and hepatitis B envelope antigen[5].
OSS_128167 细胞实验
Cell Line
Concentration
Treated Time
Description
References
H9c2 cells
20 and 50 µM
1 hour
To evaluate the effects of OSS-128167 on HG-induced fibrosis and apoptosis in H9c2 cells. Results showed that OSS-128167 significantly increased the expression of fibrotic markers COL-1 and TGF-β, and apoptotic proteins Bax and cle-PARP, while decreasing Bcl-2 expression.
Mol Med Rep. 2021 May;23(5):367.
RAW264.7 cells
200 µM
24 hours
Inhibition of SIRT6 activity promotes M1 macrophage polarization and suppresses M2 polarization
Cell Biosci. 2021 Dec 14;11(1):210.
Bone marrow-derived macrophages (BMDM)
200 µM
24 hours
Inhibition of SIRT6 activity reduces migration and phagocytosis capacity of macrophages
Cell Biosci. 2021 Dec 14;11(1):210.
BV2 cells
20 µM
24 hours
CAPE pretreatment reduces ROS generation and promotes M1 to M2 microglia polarization via activating the Sirt6/Nrf2 pathway in H2O2-induced BV2 cells.But this effect could be significantly inhibited by OSS_128167.
Antioxidants (Basel). 2023 Mar 13;12(3):714.
CD38+ NK cells
50 µM
24 hours
C3G significantly increased Sirtuin 6 (Sirt6) expression and TNF-α level, and decreased natural killer group 2D (NKG2D) expression and IFN-γ level
Arthritis Res Ther. 2019 Oct 28;21(1):220.
H9c2 cells
100 µM
24 hours
OSS_128167 inhibited H9c2 cell proliferation and promoted apoptosis, while increasing ROS, SA-β-galactosidase, and HK2 levels and decreasing TERT expression.
Aging (Albany NY). 2022 Dec 6;14(23):9730-9757.
Human podocytes
100 µM
24 hours
Inhibit Sirt6 expression, exacerbate high glucose-induced podocyte cytoskeletal remodeling and apoptosis
Ren Fail. 2024 Dec;46(2):2410396.
HepG2-NTCP cells
100 µM
3 days
To evaluate the antiviral effect of OSS_128167 on HBV transcription and replication. Results showed that OSS_128167 significantly reduced the levels of HBV core DNA and 3.5-Kb RNA, and inhibited the secretion of HBsAg and HBeAg.
Front Pharmacol. 2019 Oct 25;10:1270.
HepG2.2.15 cells
100 µM
3 days
To evaluate the antiviral effect of OSS_128167 on HBV transcription and replication. Results showed that OSS_128167 significantly reduced the levels of HBV core DNA and 3.5-Kb RNA, and inhibited the secretion of HBsAg and HBeAg.
Front Pharmacol. 2019 Oct 25;10:1270.
Primary DLBCL cells
80 µM
48 hours
To evaluate the effect of OSS_128167 on apoptosis in primary DLBCL cells, results showed significant increase in apoptosis rate
J Exp Clin Cancer Res. 2020 Jul 25;39(1):142.
LY8 cells
100 µM
48 hours
To evaluate the effect of OSS_128167 on DLBCL cell viability, results showed significant reduction in cell viability after 48 hours
J Exp Clin Cancer Res. 2020 Jul 25;39(1):142.
LY1 cells
100 µM
48 hours
To evaluate the effect of OSS_128167 on DLBCL cell viability, results showed significant reduction in cell viability after 48 hours
J Exp Clin Cancer Res. 2020 Jul 25;39(1):142.
Mononuclear cells (MNCs)
50 µM
48 hours
C3G stimulated MNCs to increase IL-2 and IL-10 production and the Treg cell proportion, and it decreased IL-6 and IFN-γ production and the CD38+ NK cell proportion
Arthritis Res Ther. 2019 Oct 28;21(1):220.
RA synovial fibroblasts (RASFs)
50 µM
C3G significantly increased RASF apoptosis and decreased RASF proliferation and IL-6 production in the culture medium
Arthritis Res Ther. 2019 Oct 28;21(1):220.
OSS_128167 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Acute severe asthma (ASA) and chronic severe asthma (CSA) models
Intraperitoneal injection
10 mg/kg
Administered 2 h before HDM/LPS challenge
To evaluate the effect of OSS_128167 on airway inflammation and remodeling, results showed that OSS_128167 significantly attenuated airway inflammation and remodeling.
Nat Commun. 2023 Dec 22;14(1):8525
BALB/c nude mice
MDA-MB-231 tumor model
Intraperitoneal injection
20 and 40 mg/kg
Once daily for 2 weeks
To evaluate the anti-tumor effect of icariin in vivo, results showed that icariin significantly inhibited the growth of MDA-MB-231 tumors.
Cancer Sci. 2020 Nov;111(11):4242-4256.
C57BL/6 mice
Streptozotocin (STZ)-induced type 1 diabetic cardiomyopathy model
Oral gavage
20 or 50 mg/kg
Every other day for 16 weeks
To evaluate the effects of OSS-128167 on diabetic cardiomyopathy. Results showed that OSS-128167 aggravated diabetes-induced myocardial fibrosis and apoptosis, increased the expression of inflammatory factor TNF-α and oxidative stress levels.
Mol Med Rep. 2021 May;23(5):367.
Sprague Dawley (SD) rats
Bovine type II collagen-induced arthritis (CIA)
Tail vein injection
25 mg/kg
Twice per week for six consecutive administrations
C3G injection significantly alleviated CIA, increased IL-10 level and Treg cell proportion, and decreased IL-6 and IFN-γ levels and CD38+ NK cell proportion
Arthritis Res Ther. 2019 Oct 28;21(1):220.
HBV transgenic mice
HBV transgenic mouse model
Intraperitoneal injection
50 mg/kg
Every 4 days for 12 days
To evaluate the antiviral effect of OSS_128167 in vivo. Results showed that OSS_128167 significantly reduced the levels of HBV DNA, HBsAg, and HBeAg in serum, and inhibited the expression of intrahepatic HBV DNA and RNA.
Front Pharmacol. 2019 Oct 25;10:1270.
C57BL/6 male mice
LPS-induced ARDS model
Intraperitoneal injection
80 mg/kg
Single dose, lasting 24 hours
To investigate the effect of OSS_128167 on LPS-induced ARDS. Results showed that OSS_128167 significantly accelerated LPS-induced loss of tight junction proteins, lung inflammation, and apoptosis, and activated the ERK1/2 pathway while inhibiting lung autophagy.
Int J Med Sci. 2023 Mar 5;20(5):581-594.
SCID beige mice
DLBCL xenograft model
Intraperitoneal injection
80 mg/kg
Every 2 days for 2 weeks
To evaluate the effect of OSS_128167 on tumor growth in DLBCL xenograft model, results showed significant suppression of tumor growth
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