SR-18292

SKU: orb1302925

Description

SR-18292 is a small molecule inhibitor that targets PGC-1α, promoting its acetylation to suppress hepatic gluconeogenesis. This mechanism reduces glucose output in hepatocytes, making it a useful research tool for studying metabolic disorders like type 2 diabetes in both cellular and animal models.

Research Area

Cell Biology, Metabolism Research

Key Properties

• CAS Number: 2095432-55-4
• MW: 366.5
• Purity: 99.91% (May vary between batches)
• Formula: C₂₃H₃₀N₂O₂
• SMILES: Cc1ccc(CN(CC(O)COc2cccc3[nH]ccc23)C(C)(C)C)cc1
• Target: Autophagy,PGC-1α
• Solubility: H2O:Insoluble;Ethanol:10 mg/mL (27.29 mM);DMSO:245 mg/mL (668.49 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.46 mM)

Bioactivity

• Target IC50:
  PGC1α:NA
• In Vivo:
  SR-18292 notably lowers fasting blood glucose levels, enhances hepatic insulin sensitivity, and ameliorates glucose homeostasis in diabetic mice. When administered to mice fed a high-fat diet (HFD)—a model for studying obesity and Type 2 Diabetes (T2D)—through intraperitoneal (I.P.) injection at a dose of 45 mg/kg for three consecutive days, with an additional dose on the fourth day, SR-18292 demonstrates significant reductions in fasting blood glucose levels compared to those in vehicle-treated control mice. Furthermore, SR-18292 treatment notably inhibits the expression of gluconeogenic genes, particularly Pck1, in the livers of these mice, indicating a suppression of a key regulatory pathway responding to fasting.
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• In Vitro:
  SR-18292 enhances the association between the transcriptional coactivator PGC-1α and the acetyltransferase GCN5, thereby increasing the acetylation of specific lysine residues on PGC-1α. This modification potentially reduces PGC-1α's gluconeogenic activity by diminishing its ability to co-activate the nuclear hormone receptor HNF4α, subsequently suppressing the gluconeogenic transcriptional function of the HNF4α/PGC-1α complex. This mechanism signifies SR-18292's role in modulating energy homeostasis through the regulation of fat and glucose metabolism by influencing PGC-1α's interaction with key metabolic regulatory proteins.
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• Cell Research:
  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[
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• Animal Research:
  SR-18292 is re-suspended in a 10% DMSO/10% Tween80/80% PBS solution at a final concentration of 6-12 mg/mL.MiceFor 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
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Autophagy, Inhibitor, inhibit, SR 18292, SR18292, SR-18292, PGC-1α, PPARγ coactivator-1α

Compound Identifiers

PubChem CID

129896798