| 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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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
SR-18292 is a potent inhibitor of PPAR gamma coactivator-1α (PGC-1α), a transcriptional coactivator involved in gluconeogenesis and energy metabolism. It increases the interaction of PGC-1α with GCN5 and reduces co-activation of HNF4α by PGC-1α. By inhibiting PGC-1α, SR-18292 suppresses gluconeogenic gene expression and reduces glucose production in hepatocytes. Its mechanism involves modulation of PGC-1α acetylation and interaction with GCN5.
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| ln Vitro |
PGC-1α, a transcriptional coactivator, co-activates transcription factors that control glucose and fat metabolism, which is essential for maintaining energy homeostasis. PGC-1α's association with the acetyl transferase GCN5 is enhanced by SR-18292, whilst PGC-1α's co-activation of the nuclear hormone receptor HNF4α is decreased. The gluconeogenic transcriptional function of HNF4α/PGC-1α is suppressed by SR-18292. SR-18292 enhances the interaction between GCN5 and PGC-1α, leading to the acetylation of particular lysine residues in PGC-1α. This process may potentially reduce the gluconeogenic activity of PGC-1α.
In vitro, SR-18292 increases PGC-1α acetylation, suppresses gluconeogenic gene expression, and reduces glucose production in hepatocytes. It increases the interaction of PGC-1α with GCN5 and reduces co-activation of HNF4α by PGC-1α. Its in vitro activity is characterized by potent inhibition of PGC-1α and suppression of gluconeogenesis. SR-18292 is a potent inhibitor of PGC-1α. |
| ln Vivo |
In diabetic mice, SR-18292 lowers fasting blood glucose, boosts hepatic insulin sensitivity, and enhances glucose homeostasis. A dietary model of obesity and type 2 diabetes (T2D) using mice on a high-fat diet (HFD) are administered SR-18292 (45 mg/kg) by IP injection for three days in a row, and then again on the fourth day, prior to the measurement of fasting blood glucose. Surprisingly, SR-18292-treated animals exhibit noticeably lower fasting blood glucose concentrations than control mice given the same vehicle. One regulating aspect of the body's reaction to fasting is the activation of gluconeogenic gene expression. Importantly, livers removed from mice given SR-18292 treatment exhibit decreased gluconeogenic gene expression, particularly that of Pck1[1].
In vivo, SR-18292 reduces blood glucose, strongly increases hepatic insulin sensitivity, and improves glucose homeostasis in dietary and genetic mouse models of type 2 diabetes (T2D). It has been shown to have beneficial effects in dietary and genetic mouse models of T2D. Its in vivo efficacy is attributed to its ability to inhibit PGC-1α and suppress gluconeogenesis. |
| Enzyme Assay |
For determination of GCN5 HAT activity U-2 OS cells overexpressing Ad-GCN5 are treated with SR-18292 (10 μM) for 18 h. Cells are lysed with buffer B (20 mM HEPES-KOH (pH 7.9), 125 mM NaCl, 1 mM EDTA, 1 mM DTT, 1% IGEPAL (v/v), 10% glycerol (v/v), 5 mM NaF, 5 mM β-glycerophosphate, 5 mM sodium butyrate and 10 mM nicotinamide), supplemented with Protease Inhibitor Cocktail. FLAG-GCN5 is immunoprecipitated with FLAG beads overnight at 4°C following multiple washes with lysis buffer. GCN5 is then eluted using 3× FLAG peptide and the purified protein is used to determine HAT activity using the HAT Inhibitor Screening Assay Kit[1]. |
| Cell Assay |
For cell viability determination using MTT, primary hepatocytes are seeded on a 96-well plate at 20,000 cells/well. The following day cells are treated at different doses, as indicated, for 18 h treatment of primary hepatocytes. 5 μL of MTT reagent (5 mg/mL) is then added to each well (n=4/dose) and cells are incubated for 1h at 37°C. Medium is discarded and dye is extracted by adding 100 μL DMSO to each well. For cytotoxicity determination using ToxiLight Non-destructive Cytotoxicity Bioassay, hepatocytes are seeded on a 6-well plate and treated with either SR-18292 (20 μM) or Cisplatin (50 μM) for 18 h. 50 μL of medium is collected and used to measure cellular toxicity by adding 100 of adenylate kinase detection reagent and incubating 5 min at RT before measuring luminescence[1]. |
| Animal Protocol |
Mice[1] For in vivo studies with DIO mice, males 6-8 weeks old are fed high fat diet (HFD) for the indicated time. For drug administration, SR-18292 (45 mg/kg) is injected via I.P. for 3 days between 4-5 pm and food is removed on day 3 at 5pm. The following morning (day 4) SR-18292 is injected again (for a total of 4 injections) and blood glucose is measured after 3 hours. Injection volume does not exceed 275 μL per mouse[1]. |
| ADME/Pharmacokinetics |
SR-18292 has a molecular formula of C27H25N5O3 and a molecular weight of 467.52. Its CAS number is 2095432-55-4. The compound is a potent inhibitor of PGC-1α. It increases PGC-1α acetylation, suppresses gluconeogenic gene expression, and reduces glucose production. SR-18292 has been shown to reduce blood glucose and improve glucose homeostasis in mouse models of T2D.
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| Toxicity/Toxicokinetics |
SR-18292 is a PGC-1α inhibitor with a well-characterized mechanism of action. As with any metabolic modulator, potential toxicity may include effects on energy metabolism and glucose homeostasis. The compound's safety profile should be evaluated in preclinical toxicology studies. SR-18292 is for research use only and is not approved for human therapeutic use. It represents a valuable tool for studying PGC-1α biology and diabetes.
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| References | |
| Additional Infomation |
SR-18292 (CAS# 2095432-55-4) is a potent inhibitor of PPAR gamma coactivator-1α (PGC-1α). It increases PGC-1α acetylation, suppresses gluconeogenic gene expression, and reduces glucose production in hepatocytes. SR-18292 reduces blood glucose, increases hepatic insulin sensitivity, and improves glucose homeostasis in T2D mouse models. The compound is for research use only and not for human therapeutic use.
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| Molecular Formula |
C23H30N2O2
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| Molecular Weight |
366.496506214142
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| Exact Mass |
366.23
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| Elemental Analysis |
C, 75.37; H, 8.25; N, 7.64; O, 8.73
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| CAS # |
2095432-55-4
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| PubChem CID |
129896798
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| Appearance |
White to light brown solid powder
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
27
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| Complexity |
442
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC=C(C=C1)CN(CC(COC2=CC=CC3=C2C=CN3)O)C(C)(C)C
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| InChi Key |
BNRANURXPKRRKP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H30N2O2/c1-17-8-10-18(11-9-17)14-25(23(2,3)4)15-19(26)16-27-22-7-5-6-21-20(22)12-13-24-21/h5-13,19,24,26H,14-16H2,1-4H3
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| Chemical Name |
1-((1H-indol-4-yl)oxy)-3-(tert-butyl(4-methylbenzyl)amino)propan-2-ol
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| Synonyms |
SR18292 SR-18292 SR 18292
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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) |
Ethanol : ~100 mg/mL (~272.85 mM)
DMSO : ≥ 100 mg/mL (~272.85 mM) H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.82 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 25.0 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: ≥ 2.5 mg/mL (6.82 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 25.0 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: ≥ 2.5 mg/mL (6.82 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 | 2.7285 mL | 13.6426 mL | 27.2851 mL | |
| 5 mM | 0.5457 mL | 2.7285 mL | 5.4570 mL | |
| 10 mM | 0.2729 mL | 1.3643 mL | 2.7285 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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