Mifobate

Mifobate (SR-202) is a potent and specific PPARγ antagonist. Mifobate (SR-202) selectively inhibits Thiazolidinedione (TZD)-induced PPARγ transcriptional activity (IC₅₀=140 μM). Mifobate (SR-202) does not affect basal or ligand-stimulated transcriptional activity of PPARα, PPARβ, or the farnesoid X receptor (FXR). Mifobate (SR-202) shows antiobesity and antidiabetic effects^[1]. In Vitro: Mifobate (100-400 μM; pretreated with 24 hours) significantly inhibits BRL 49653- and hormone-induced adipocyte differentiation of 3T3-L1 cells in a dose-dependent manner after 6 days^[1].
Mifobate is able to both interact specifically with PPARγ and inhibit its agonist-dependent interaction with the coactivator steroid receptor coactivator-1 (SRC-1). Mifobate (SR-202) inhibits TZD-stimulated recruitment of the coactivator steroid receptor coactivator-1. Mifobate blocks adipocyte differentiation induced either by thiazolidinediones or by the combination of dexamethasone, insulin, and 3-isobutyl-1-methylxanthine (IBMX)^[1]. In Vivo: Mifobate (400 mg/kg; Feed for 20 days) increases insulin sensitivity in ob/ob mice^[1]