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SR 2595 is an inverse agonist of PPARγ (IC50 = 30 nM) that represses both transactivation in a promoter:reporter assay and expression of the adipogenic marker fatty acid-binding protein 4 in differentiating murine preadipocytes. Repression of PPARγ with SR 2595 promotes osteogenesis, as measured by calcium phosphatase deposition, in cultured human mesenchymal stem cells (MSCs). SR 2595 also increases expression of bone morphogenetic proteins BMP2 and BMP6 in MSCs. | [in vitro]
sr 2595 was identified as an inverse agonist of pparγ that repressed both transactivation and expression of the adipogenic marker fatty acid-binding protein 4 in differentiating murine preadipocytes. moreover, the repression of pparγ with sr 2595 promoted osteogenesis in cultured human mesenchymal stem cells (mscs), as demonstrated by calcium phosphatase deposition. in addition, sr 2595 could also increase the expression of bone morphogenetic proteins bmp2 and bmp6 in mscs [1]. | [in vivo]
to determine whether pharmacological pparg repression would impair insulin sensitivity, sr2595 was administered chronically to lean c57bl/6j mice. the pk properties of sr2595 were sufficient to support once daily oral dosing at 20 mg/kg. lean c57bl/6j mice treated with sr2595 showed no significant change in insulin sensitivity as measured by insulin tolerance test, nor fasting insulin levels. in addition, no change in food consumption or body weight was observed during the treatment period [1]. | [IC 50]
30 nm | [storage]
Store at -20°C | [References]
[1] marciano, d. p.,kuruvilla, d.s.,boregowda, s.v., et al. pharmacological repression of pparγ promotes osteogenesis. nature communications 6, 1-7 (2015). |
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