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Chemical Structure| 887686-02-4 Chemical Structure| 887686-02-4

Structure of OSS_128167
CAS No.: 887686-02-4

Chemical Structure| 887686-02-4

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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.

Synonyms: OSS-128167; SIRT6-IN-1

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Product Details of OSS_128167

CAS No. :887686-02-4
Formula : C19H14N2O6
M.W : 366.32
SMILES Code : O=C(O)C1=CC(NC(C2=CC=CC(NC(C3=CC=CO3)=O)=C2)=O)=CC=C1O
Synonyms :
OSS-128167; SIRT6-IN-1
MDL No. :MFCD07114226
InChI Key :HTJWLEGCECXGSQ-UHFFFAOYSA-N
Pubchem ID :6496840

Safety of OSS_128167

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315
Precautionary Statements:P264-P280-P302+P352-P332+P313-P362

Related Pathways of OSS_128167

epigenetics

Isoform Comparison

Biological Activity

Target
  • SIRT1

    SIRT1, IC50:1578 μM

  • SIRT2

    SIRT2, IC50:751 μM

  • SIRT6

    SIRT6, IC50:89 μM

In Vitro:

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.

In Vivo:

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 J Exp Clin Cancer Res. 2020 Jul 25;39(1):142.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.73mL

0.55mL

0.27mL

13.65mL

2.73mL

1.36mL

27.30mL

5.46mL

2.73mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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