| Bioactivity | SR-18292 is a PPAR gamma coactivator-1α (PGC-1α) inhibitor, which increases PGC-1α acetylation, suppresses gluconeogenic gene expression and reduces glucose production in hepatocytes. | ||||||||||||
| Target | PGC-1α | ||||||||||||
| Invitro | The transcriptional coactivator PGC-1α plays a pivotal role in energy homeostasis by co-activating transcription factors that regulate fat and glucose metabolism. SR-18292 increases the interaction of PGC-1α with the acetyl transferase GCN5 and reduces co-activation of nuclear hormone receptor HNF4α by PGC-1α. SR-18292 suppresses HNF4α/PGC-1α gluconeogenic transcriptional function. By increasing the interaction of GCN5 with PGC-1α, SR-18292 increases the acetylation of specific PGC-1α lysine residues that might subsequently decrease its gluconeogenic activity[1]. | ||||||||||||
| In Vivo | SR-18292 reduces fasting blood glucose, increases hepatic insulin sensitivity and improves glucose homeostasis in diabetic mice. The high fat diet (HFD) fed mice, a dietary model of obesity and T2D, are treated with SR-18292 (45mg/kg) via I.P. injection for 3 consecutive days and again on day 4 before measuring fasting blood glucose. Strikingly, mice that are treated with SR-18292 have significantly lower levels of fasting blood glucose concentrations compared to matched vehicle-treated control mice. The induction of gluconeogenic gene expression is a regulatory component of the response to fasting. Importantly, gluconeogenic gene expression, specifically that of Pck1, is inhibited in livers isolated from mice treated with SR-18292[1]. | ||||||||||||
| Name | SR-18292 | ||||||||||||
| CAS | 2095432-55-4 | ||||||||||||
| Formula | C23H30N2O2 | ||||||||||||
| Molar Mass | 366.50 | ||||||||||||
| Appearance | Oil | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Sharabi K, et al. Selective Chemical Inhibition of PGC-1α Gluconeogenic Activity Ameliorates Type 2 Diabetes. Cell. 2017 Mar 23;169(1):148-160.e15. |