RG-12525 is a a specific, competitive and orally effective antagonist of the peptidoleukotrienes , LTC4 , LTD4 and LTE4 , inhibiting LTC4-, LTD4- and LTE4-inducd guinea pig parenchymal strips contractions, with IC 50 s of 2.6 nM, 2.5 nM and 7 nM, respectively; RG-12525 is also a peroxisome proliferator-activated receptor gamma ( PPAR-gamma ) agonist with IC 50 of appr 60 nM and a potent inhibitor of CYP3A4 , with a K i value of 0.5 µM. In Vitro RG 12525 competitively inhibits 3 H-LTD4 binding to lung membranes (K i = 3.0 +/- 0.3 nM) and competitively antagonizes the spasmogenic activity of LTC4, LTD4 and LTE4 on lung strips (KB values = 3 nM) with greater than 8000 fold selectivity. RG 12525 (2.5 µM or 25 µM) inhibits the microsomal activity of CYP2C9 and -3A4, but does not significantly inhibit CYP1A2,-2A6, -2C19, or -2D6. RG 12525 (25 µM) also causes a substantial amount of inhibition at the 5 and 10 µM midazolam concentrations. MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo RG 12525 orally inhibits LTD4 induced wheal formation (ED 50 = 5 mg/kg with a t 1/2 = 10 hrs at 9 mg/kg), LTD4 induces bronchoconstriction (ED 50 = 0.6 mg/kg), and anaphylactic death (ED 50 = 2.2 mg/kg with a t 1/2 = 7 hrs at 10 mg/kg) and antigen induces bronchoconstriction (ED 50 = 0.6 mg/kg) . RG 12525 inhibits antigen-induced mortality in the systemic anaphylaxis model with an ED 50 (95% confidence interval) = 2.2 (0.8-6.4) mg/kg. RG 12525 also protects against LTD4-induced bronchoconstriction in a model measuring changes in pulmonary function with an ED 50 = 0.6 (0.4-1.0) mg/kg. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Form:Solid IC50& Target:IC50: appr 60 nM (PPAR-γ)