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Purity: ≥98%
OSS_128167 (formerly SIRT6-IN-1) is a novel, potent and selective SIRT6 inhibitor with IC50 of 89, 1578 and 751 μM for SIRT6, SIRT1 and SIRT2, respectively. Although OSS_128167 inhibits SIRT6 in the micromolar range, it shows excellent selectivity, as its IC50 value for SIRT6 is approximately 17 times lower in comparison to the IC50 for SIRT1 and 9 times lower than SIRT2. OSS_128167 at 200 μM induces chemosensitization in primary multiple myeloma (MM) cells (NCI-H929), as well as in melphalan-resistant (LR-5) and doxorubicin-resistant (Dox40) MM cell line.
| ln Vitro |
OSS_128167 (Compound 9; 100 μM; 0–24 hours; BxPC3 cells) treatment raises the acetylation of H3K9. and also caused BxPC-3 cells to express more GLUT-1 [1]. Phenol myristate acetate (PMA)-induced TNF-α secretion in cultured BxPC-3 cells was effectively inhibited by OSS_128167 (Compound 9). Cellular uptake of glucose is enhanced by OSS_128167 [1]. HepG2.2.15 and HepG2-NTCP cells treated with 100 μM of OSS_128167 for 96 hours showed a significant reduction in HBV core DNA and 3.5-Kb RNA levels. Additionally, OSS_128167 treatment reduced the expression of HBsAg in cell lysates as well as the secretion of HBsAg and HBeAg, the hepatitis B surface antigens [2]. MM cell lines that are melphalan-resistant (LR-5) and doxorubicin-resistant (Dox40) as well as primary multiple myeloma (MM) cells (NCI-H929) are chemosensitized by OSS_128167 (200 μM)[3].
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| ln Vivo |
HBV transgenic mice's HBV DNA and 3.5-Kb RNA levels were markedly suppressed by treatment with OSS_128167 (50 mg/kg; intraperitoneal injection; every 4 days; for 12 days; male HBV transgenic mice) [2].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: BxPC3 cells Tested Concentrations: 100 µM Incubation Duration: 0 hrs (hours), 2 hrs (hours), 6 hrs (hours), 18 hrs (hours), 24 hrs (hours) Experimental Results: Increased H3K9 acetylation. RT-PCR[2] Cell Types: HepG2.2.15 and HepG2-sodium taurocholate cotransporting polypeptide (NTCP) cells Tested Concentrations: 100 µM Incubation Duration: 96 hrs (hours) Experimental Results: Dramatically diminished HBV core DNA and 3.5-Kb RNA levels. |
| Animal Protocol |
Animal/Disease Models: Male HBV transgenic mice (6-8weeks old)[2]
Doses: 50 mg/kg Route of Administration: intraperitoneal (ip)injection; every 4 days; for 12 days Experimental Results: The level of HBV DNA and 3.5-Kb RNA were markedly suppressed in HBV transgenic mice. |
| References |
[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 α. 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. |
| Molecular Formula |
C19H14N2O6
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| Molecular Weight |
366.32
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| CAS # |
887686-02-4
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| SMILES |
C1=CC(NC(=O)C2=CC=CO2)=CC(C(=O)NC2=CC=C(O)C(C(O)=O)=C2)=C1
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7299 mL | 13.6493 mL | 27.2985 mL | |
| 5 mM | 0.5460 mL | 2.7299 mL | 5.4597 mL | |
| 10 mM | 0.2730 mL | 1.3649 mL | 2.7299 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
J Med Chem.2014 Jun 12;57(11):4796-804. |
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SIRT6 depletion/inhibition sensitizes MM cells to genotoxic agents.Blood. 2016 Mar 3; 127(9): 1138–1150. |
SIRT6 plays multiple roles in the DDR of MM cells.Blood. 2016 Mar 3; 127(9): 1138–1150. |
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