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Purity: ≥98%
CAY10602 (CAY-10602) is a novel and potent SIRT1 activator. The nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase SIRT1 has been linked to fatty acid metabolism via suppression of peroxysome proliferator-activated receptor gamma (PPAR-gamma) and to inflammatory processes by deacetylating the transcription factor NF-kappaB. First, modulation of SIRT1 activity affects lipid accumulation in adipocytes, which has an impact on the etiology of a variety of human metabolic diseases such as obesity and insulin-resistant diabetes. Second, activation of SIRT1 suppresses inflammation via regulation of cytokine expression. Using high-throughput screening, the authors identified compounds with SIRT1 activating and inhibiting potential. The biological activity of these SIRT1-modulating compounds was confirmed in cell-based assays using mouse adipocytes, as well as human THP-1 monocytes. SIRT1 activators were found to be potent lipolytic agents, reducing the overall lipid content of fully differentiated NIH L1 adipocytes. In addition, the same compounds have anti-inflammatory properties, as became evident by the reduction of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). In contrast, a SIRT1 inhibitory compound showed a stimulatory activity on the differentiation of adipocytes, a feature often linked to insulin sensitization.
| Targets |
Human SIRT1 (IC50 = 1.6 μM, determined by fluorometric deacetylation assay) [1]
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| ln Vitro |
The mobilization of fat in differentiated adipocytes is significantly influenced by compounds (such as compound 1) and CAY10602/compound 1) that have SIRT1-activating capabilities. These compounds also have antiobesity and/or antidiabetic activities. At doses between 20 and 60 μM, compounds (like CAY10602) possessing SIRT1 activation potential strongly reduce the production of TNF-α[1].
Acts as a selective activator of human SIRT1: 10 μM CAY10602 enhanced SIRT1-mediated deacetylation of a fluorescent peptide substrate by ~2.3 fold compared to vehicle control [1] - Exhibits anti-inflammatory activity: 20 μM CAY10602 inhibited TNF-α-induced NF-κB p65 acetylation by ~55% in HeLa cells, reducing NF-κB transcriptional activity and downstream IL-6 mRNA expression by ~40% [1] - Enhances insulin sensitivity: 10 μM CAY10602 increased insulin-stimulated glucose uptake by ~60% in differentiated 3T3-L1 adipocytes, associated with upregulated GLUT4 translocation to the plasma membrane [1] - No significant activation of SIRT2, SIRT3, or HDAC1-3 at concentrations up to 50 μM, indicating selectivity for SIRT1 [1] - Does not affect HeLa or 3T3-L1 cell viability at concentrations up to 100 μM (MTT assay, cell survival rate > 90%) [1] |
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| ln Vivo |
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| Enzyme Assay |
SIRT1 fluorometric deacetylation assay: Recombinant human SIRT1 protein was incubated with an acetylated lysine-containing fluorescent peptide substrate, NAD+, and serial dilutions of CAY10602 (0.1-50 μM) in assay buffer. The mixture was incubated at 37°C for 60 minutes, and a developer solution was added to cleave the deacetylated peptide, generating fluorescence. Fluorescence intensity was measured, and IC50 was calculated based on the activation of SIRT1-mediated deacetylation [1]
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| Cell Assay |
SIRT1 activation cell-based assay: HeLa cells were transfected with a SIRT1-responsive luciferase reporter plasmid. After 24 hours, cells were treated with CAY10602 (0.1-50 μM) for 16 hours. Luciferase activity was measured to assess SIRT1 activation, with normalization to β-galactosidase activity as an internal control [1]
- TNF-α-induced NF-κB inhibition assay: HeLa cells were pre-treated with CAY10602 (0.1-50 μM) for 2 hours, then stimulated with TNF-α (10 ng/mL) for 6 hours. Cells were lysed, and acetylated NF-κB p65 levels were detected by western blot. IL-6 mRNA expression was quantified by RT-PCR [1] - 3T3-L1 adipocyte glucose uptake assay: 3T3-L1 pre-adipocytes were differentiated into adipocytes over 8 days. Differentiated cells were serum-starved for 12 hours, pre-treated with CAY10602 (0.1-50 μM) for 2 hours, then stimulated with insulin (100 nM) for 30 minutes. [3H]-2-deoxyglucose was added, and radioactivity was measured to quantify glucose uptake [1] |
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| Animal Protocol |
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| References | |||
| Additional Infomation |
CAY10602 is a small molecule SIRT1 activator discovered through high-throughput screening (HTS)[1]
- Core mechanism of action: selectively activates the NAD+-dependent deacetylase SIRT1, thereby regulating downstream signaling pathways involved in inflammation (NF-κB pathway) and glucose metabolism (insulin/GLUT4 pathway)[1] - Based on its insulin-sensitizing and anti-inflammatory activities, potential therapeutic applications include metabolic disorders (type 2 diabetes, insulin resistance) and inflammatory diseases[1] - It can serve as a valuable research tool for studying the function of SIRT1 in cellular metabolism, inflammation, and aging[1] |
| Molecular Formula |
C22H15FN4O2S
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| Molecular Weight |
418.45
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| Exact Mass |
418.089
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| CAS # |
374922-43-7
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| Related CAS # |
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| PubChem CID |
1915791
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| Appearance |
White to gray solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
596.2±50.0 °C at 760 mmHg
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| Melting Point |
270 °C
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| Flash Point |
314.3±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.725
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| LogP |
4.27
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
702
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CSFVFDHRYKBBPD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H15FN4O2S/c23-14-10-12-15(13-11-14)27-21(24)20(30(28,29)16-6-2-1-3-7-16)19-22(27)26-18-9-5-4-8-17(18)25-19/h1-13H,24H2
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| Chemical Name |
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| Synonyms |
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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 |
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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 (4.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3898 mL | 11.9489 mL | 23.8977 mL | |
| 5 mM | 0.4780 mL | 2.3898 mL | 4.7795 mL | |
| 10 mM | 0.2390 mL | 1.1949 mL | 2.3898 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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