WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 407880
Description: OSS-128167, also known as SIRT6-IN-1, is a potent and selective SIRT 6 inhibitor (SIRT6; IC50 = 89 μM). OSS-128167 Restricts Hepatitis B Virus Transcription and Replication Through Targeting Transcription Factor Peroxisome Proliferator-Activated Receptors α. OSS_128167 exerted excellent anti-lymphoma effects via inhibiting PI3K/Akt/mTOR signaling.
MedKoo Cat#: 407880
Chemical Formula: C19H14N2O6
Exact Mass: 366.0852
Molecular Weight: 366.33
Elemental Analysis: C, 62.30; H, 3.85; N, 7.65; O, 26.20
Synonym: OSS-128167; OSS 128167; OSS128167; SIRT6-IN-1; OSS_128167;
IUPAC/Chemical Name: 5-(3-(furan-2-carboxamido)benzamido)-2-hydroxybenzoic acid
InChi Key: HTJWLEGCECXGSQ-UHFFFAOYSA-N
InChi Code: InChI=1S/C19H14N2O6/c22-15-7-6-13(10-14(15)19(25)26)20-17(23)11-3-1-4-12(9-11)21-18(24)16-5-2-8-27-16/h1-10,22H,(H,20,23)(H,21,24)(H,25,26)
SMILES Code: C1=CC(NC(=O)C2=CC=CO2)=CC(C(=O)NC2=CC=C(O)C(C(O)=O)=C2)=C1
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||SIRT 6 inhibitor (SIRT6; IC50 = 89 μM)|
|In vitro activity:||Real-time PCR results revealed that OSS_128167 significantly decreased HBV core DNA level, as confirmed by southern blotting analysis. The level of 3.5-Kb RNA was also modestly decreased after treated with OSS_128167. Similar to its effect on HBV core DNA and 3.5-Kb RNA levels, OSS_128167 treatment also inhibited hepatitis B surface antigen (HBsAg) and hepatitis B envelope antigen (HBeAg) secretions, as well as HBsAg expression in cell lysates. These results above implied that SIRT6 inhibitor OSS_128167 might serve as a potential drug for HBV therapeutics. (reference: Front Pharmacol. 2019; 10: 1270)|
|In vivo activity:||Antiviral Activity of OSS_128167 in Hepatitis B Virus Transgenic Mouse Model: OSS_128167 showed strong antiviral effect. treatment with OSS_128167 resulted in a marked reduction of intrahepatic HBV DNA, total HBV RNAs and 3.5-Kb RNA level at the end of treatment. By contrast, ETV treatment had no effect on HBV RNA level. Immunohistochemical analysis also showed that OSS_128167 suppressed HBV core protein expression in liver tissues. Taken together, these data showed that OSS_128167 could inhibit HBV transcription and replication in vivo, indicating OSS_128167 might serve as a new therapeutic strategy for HBV treatment. (reference: Front Pharmacol. 2019; 10: 1270) The anti-tumor impact of OSS_128167 on DLBCL cells was further investigated in vivo using a xenograft model of SCID beige mice. Consistent with our in vitro results, obviously decreased tumor growth was noted in the mice treated with OSS_128167 in contrast to the vehicle control group. Additionally, lower expression level of the proliferative marker Ki-67 was observed in OSS_128167 exposed mice. This experiment for the first time performed intraperitoneal inoculation of OSS_128167 onto mice. OSS_128167, a novel targeted inhibitor of Sirt6, exerted excellent anti-lymphoma effects via inhibiting PI3K/Akt/mTOR signaling. In addition, blockade of Sirt6 expression enhanced the sensitivity of DLBCL cells to chemotherapeutic agents. These findings provide mechanistic insights into the oncogenic activity of Sirt6 and highlight the potency of OSS_128167 for novel therapeutic strategies in DLBCL. (reference: J Exp Clin Cancer Res. 2020; 39: 142.)|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 366.33 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|Formulation protocol:||1. Damonte, P., Sociali, G., Parenti, M.D., et al. SIRT6 inhibitors with salicylate-like structure show immunosuppressive and chemosensitizing effects. Bioorg. Med. Chem. 25(20), 5849-5858 (2017). 2. Zuo, Y., Huang, L., Enkhjargal, B., et al. Activation of retinoid X receptor by bexarotene attenuates neuroinflammation via PPARγ/SIRT6/FoxO3a pathway after subarachnoid hemorrhage in rats. J. Neuroinflammation 16(1):47, (2019).|
|In vitro protocol:||Jiang H, Cheng ST, Ren JH, Ren F, Yu HB, Wang Q, Huang AL, Chen J. SIRT6 Inhibitor, OSS_128167 Restricts Hepatitis B Virus Transcription and Replication Through Targeting Transcription Factor Peroxisome Proliferator-Activated Receptors α. Front Pharmacol. 2019 Oct 25;10:1270. doi: 10.3389/fphar.2019.01270. PMID: 31708789; PMCID: PMC6823301.|
|In vivo protocol:||Jiang H, Cheng ST, Ren JH, Ren F, Yu HB, Wang Q, Huang AL, Chen J. SIRT6 Inhibitor, OSS_128167 Restricts Hepatitis B Virus Transcription and Replication Through Targeting Transcription Factor Peroxisome Proliferator-Activated Receptors α. Front Pharmacol. 2019 Oct 25;10:1270. doi: 10.3389/fphar.2019.01270. PMID: 31708789; PMCID: PMC6823301.|
1: Jiang H, Cheng ST, Ren JH, Ren F, Yu HB, Wang Q, Huang AL, Chen J. SIRT6 Inhibitor, OSS_128167 Restricts Hepatitis B Virus Transcription and Replication Through Targeting Transcription Factor Peroxisome Proliferator-Activated Receptors α. Front Pharmacol. 2019 Oct 25;10:1270. doi: 10.3389/fphar.2019.01270. PMID: 31708789; PMCID: PMC6823301.
2: Yang J, Li Y, Zhang Y, Fang X, Chen N, Zhou X, Wang X. Sirt6 promotes tumorigenesis and drug resistance of diffuse large B-cell lymphoma by mediating PI3K/Akt signaling. J Exp Clin Cancer Res. 2020 Jul 25;39(1):142. doi: 10.1186/s13046-020-01623-w. PMID: 32711549; PMCID: PMC7382040.
3: Liu X, Yang Z, Li H, Luo W, Duan W, Zhang J, Zhu Z, Liu M, Li S, Xin X, Wu H, Xian S, Liu M, Liu C, Shen C. Chrysophanol Alleviates Metabolic Syndrome by Activating the SIRT6/AMPK Signaling Pathway in Brown Adipocytes. Oxid Med Cell Longev. 2020 Nov 12;2020:7374086. doi: 10.1155/2020/7374086. PMID: 33274005; PMCID: PMC7683138.
4: Song L, Chen X, Mi L, Liu C, Zhu S, Yang T, Luo X, Zhang Q, Lu H, Liang X. Icariin-induced inhibition of SIRT6/NF-κB triggers redox mediated apoptosis and enhances anti-tumor immunity in triple-negative breast cancer. Cancer Sci. 2020 Nov;111(11):4242-4256. doi: 10.1111/cas.14648. Epub 2020 Oct 7. PMID: 32926492; PMCID: PMC7648025.
5: Wang H, Li S, Zhang G, Wu H, Chang X. Potential therapeutic effects of cyanidin-3-O-glucoside on rheumatoid arthritis by relieving inhibition of CD38+ NK cells on Treg cell differentiation. Arthritis Res Ther. 2019 Oct 28;21(1):220. doi: 10.1186/s13075-019-2001-0. PMID: 31661005; PMCID: PMC6819496.
In cancer and aging-associated pathways, SIRT6 is crucial since it prevents genomic instability, maintains telomere integrity, and regulates metabolic homeostasis and DNA repair. SIRT6 can be considered a double-edged sword in cancer because of its dual role of both tumor suppressor and oncogene. In healthy conditions, SIRT6 either acts as a gatekeeper of DNA repair mechanisms or regulates cell survival and proliferation. Following the DNA damage, SIRT6 triggers the apoptotic process, hence it is down-regulated in several cancers. However, in other cancers, it is up-regulated, corroborating the idea that it can also act as oncogene.