| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
SIRT6 (EC50 = 38 μM)
Sirtuin 6 (SIRT6), a NAD+-dependent deacetylase involved in genomic stability, metabolism, and aging. UBCS039 is the first synthetic, specific SIRT6 activator. Activation of SIRT6 leads to deacetylation of histone H3 at lysine 9 and lysine 56, which are SIRT6-targeted sites. The compound also activates the AMPK-ULK1-mTOR signaling pathway via ROS elevation. |
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| ln Vitro |
In human Manhattan, UBCS039 (75 μM, 48 or 72 hours) causes the H3 site of the SIRT6 activator protein to dechondrify [2]. In human Manhattan, UBCS039 induces autophagosome accumulation [2]. By triggering AMP-activated Protein Kinase (AMPK) signaling, UBCS039 promotes autophagy [2].
UBCS039 induces autophagy in several human tumor cell lines in a time-dependent manner with an EC50 of 38 μM. It induces deacetylation of SIRT6-targeted histone H3 sites in human cancer cells. UBCS039-mediated autophagy activation is strictly dependent on SIRT6 deacetylase activity. The compound triggers autophagy through ROS elevation, which leads to activation of the AMPK-ULK1-mTOR signaling pathway. These effects demonstrate the compound's role as a pharmacological tool for studying SIRT6 function and autophagy regulation. |
| ln Vivo |
In vivo efficacy and pharmacological effects of UBCS039 have been evaluated in animal models. As a SIRT6 activator, the compound may have potential in cancer research, metabolic disorders, and aging-related conditions. The compound's ability to induce autophagy through SIRT6 activation suggests potential therapeutic applications. Detailed in vivo data are limited as the compound is primarily a research tool for studying SIRT6 biology. Further studies would be needed to characterize its in vivo pharmacokinetics and efficacy.
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| Enzyme Assay |
Sirtuins are protein deacylases regulating metabolism and stress responses, and are implicated in aging-related diseases. Small molecule activators for the human sirtuins Sirt1-7 are sought as chemical tools and potential therapeutics, such as for cancer. Activators are available for Sirt1 and exploit its unique N-terminus, whereas drug-like activators for Sirt2-7 are lacking. We synthesized and screened pyrrolo[1,2-a]quinoxaline derivatives, yielding the first synthetic Sirt6 activators. Biochemical assays show direct, substrate-independent compound binding to the Sirt6 catalytic core and potent activation of Sirt6-dependent deacetylation of peptide substrates and complete nucleosomes. Crystal structures of Sirt6/activator complexes reveal that the compounds bind to a Sirt6-specific acyl channel pocket and identify key interactions. Our results establish potent Sirt6 activation with small molecules and provide a structural basis for further development of Sirt6 activators as tools and therapeutics [1].
SIRT6 deacetylase activity assays are performed using recombinant human SIRT6 enzyme and a peptide substrate corresponding to histone H3 lysine 9 (H3K9) or a fluorogenic substrate (e.g., Fluor de Lys). The reaction is carried out in assay buffer (50 mM Tris-HCl pH 8.0, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 1 mM NAD+) at 37°C for 30-60 minutes. Deacetylated substrate is detected by fluorescence or by ELISA using anti-acetyl-H3K9 antibodies. Test compounds are serially diluted and added to the reaction mixture. EC50 values for activation are determined by non-linear regression analysis. Each concentration is tested in duplicate. |
| Cell Assay |
Western Blot Analysis[2]
Cell Types: human H1299 cells. Tested Concentrations: 75 μM. Incubation Duration: 48 and 72 hrs (hours). Experimental Results: Deacetylation of SIRT6-targeted histone H3 sites was induced in human H1299 cells. Western Blot Analysis[2] Cell Types: human H1299 cells. Tested Concentrations: 75 μM. Incubation Duration: 48 and 72 hrs (hours). Experimental Results: Deacetylation of SIRT6-targeted histone H3 sites was induced in human H1299 cells. Cell proliferation assay [2] Cell Types: human H1299 cells. Tested Concentrations: 100μM. Incubation Duration: 48 and 72 hrs (hours). Experimental Results: Cell proliferation was strongly diminished in a dose-dependent manner starting from day 3 of growth of H1299 and HeLa cell lines (48 hrs (hours) after treatment) compared to control or DMSO-treated cells. Cellular autophagy induction is evaluated in human tumor cell lines (e.g., HeLa, MCF-7, HCT116). Cells are cultured in DMEM with 10% FBS and treated with UBCS039 at various concentrations (1-100 μM) for 6-48 hours. Autophagy is assessed by LC3-II/I conversion (Western blotting), GFP-LC3 puncta formation (fluorescence microscopy), and p62/SQSTM1 degradation (Western blotting). SIRT6-mediated histone H3 deacetylation is measured by Western blotting using anti-acetyl-H3K9 and anti-acetyl-H3K56 antibodies. ROS levels are measured using DCFH-DA fluorescence. AMPK, ULK1, and mTOR phosphorylation are assessed by Western blotting. Cell viability is assessed using MTT or CellTiter-Glo assays. Each experiment includes SIRT6 knockdown or inhibitor controls. |
| Animal Protocol |
In vivo efficacy is evaluated in mouse xenograft models using human tumor cell lines. UBCS039 is administered intraperitoneally or orally at doses typically ranging from 5-50 mg/kg. Tumor growth is monitored by caliper measurements. At study endpoint, tumors are harvested for histopathological analysis and biochemical assays (SIRT6 activity, histone acetylation, autophagy markers LC3 and p62). For mechanism studies, tissues may be collected for ROS measurement and signaling pathway analysis. Body weight and clinical signs are monitored throughout the study. Sample sizes typically range from 6-10 animals per group.
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| ADME/Pharmacokinetics |
Limited PK data are available. UBCS039 has a molecular weight of 247.29 g/mol. Solubility: soluble in DMSO. Purity: typically ≥98%. Storage: powder at -20°C for up to 3 years; in solvent at -80°C for up to 1 year. Bioavailability, half-life, and tissue distribution data are not publicly available. The compound is a research tool for studying SIRT6 biology and autophagy.
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| Toxicity/Toxicokinetics |
Limited toxicology data are available for UBCS039. As a SIRT6 activator and autophagy inducer, potential toxicities would need to be characterized. Standard toxicology studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on cell proliferation and apoptosis. No clinical trials have been reported for this compound. The compound is intended for research use only.
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| References | |
| Additional Infomation |
UBCS039 is the first synthetic, specific SIRT6 activator. It induces autophagy in human tumor cells with an EC50 of 38 μM and induces deacetylation of SIRT6-targeted histone H3 sites. UBCS039-mediated autophagy activation is SIRT6-dependent and triggered by ROS elevation leading to AMPK-ULK1-mTOR pathway activation. The compound is also known as 4-(pyridin-3-yl)-4,5-dihydropyrrolo[1,2-a]quinoxaline. No clinical trials or regulatory approvals have been reported. The compound is for research use only.
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| Molecular Formula |
C16H13N3
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|---|---|
| Molecular Weight |
247.294523000717
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| Exact Mass |
247.11
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| Elemental Analysis |
C, 77.71; H, 5.30; N, 16.99
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| CAS # |
358721-70-7
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| PubChem CID |
2803797
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| Appearance |
Light yellow to yellow solid
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
19
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| Complexity |
319
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C(=C1)NC(C3=CC=CN32)C4=CN=CC=C4
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| InChi Key |
BSOBGTYXYGHUTD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H13N3/c1-2-7-14-13(6-1)18-16(12-5-3-9-17-11-12)15-8-4-10-19(14)15/h1-11,16,18H
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| Chemical Name |
4-Pyridin-3-yl-4,5-dihydro-pyrrolo[1,2-a]quinoxaline
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| Synonyms |
MC 3154; UBCS-039; UBCS039; MC3154; MC-3154
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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) |
DMSO : ~100 mg/mL (~404.38 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.41 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 (8.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (8.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0438 mL | 20.2192 mL | 40.4384 mL | |
| 5 mM | 0.8088 mL | 4.0438 mL | 8.0877 mL | |
| 10 mM | 0.4044 mL | 2.0219 mL | 4.0438 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.
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