RG-12525(NID 525) is an orally available, selective and competitive leukotriene D (LTD) antagonist that inhibits LTC4, LTD4 and LTE4-induced contraction of guinea pig thin-walled bands, with IC50 values of 2.6 nM, 2.5 nM, and 7 nM, respectively.RG-12525 inhibits CYP3A4, with a Ki value of 0.5 µM. RG-12525 is a novel and potent PPAR-γ agonist (IC50 value of about 60 nM) with species specificity for the study of asthma.

PPARγ:60 nM, LTD4:2.5 nM (Guinea pig), LTC4:2.6 nM (Guinea pig), LTE4:7 nM (Guinea pig), [3H]-LTD4:3.0nM ( (Ki), CYP3A4:0.5 μM (Ki)

RG-12525 competitively inhibits 3H-LTD4 binding to lung membranes (Ki = 3.0 +/- 0.3 nM) and antagonizes the spasmogenic activity of LTC4, LTD4, and LTE4 on lung strips in a competitive manner (KB values = 3 nM), displaying greater than 8000-fold selectivity[1]. 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. Additionally, at 25 µM concentration, RG-12525 causes substantial inhibition at the 5 and 10 µM midazolam concentrations[3].

Orally, RG-12525 inhibits LTD4-induced wheal formation with an ED50 of 5 mg/kg and a half-life (t1/2) of 10 hours at 9 mg/kg. It also inhibits LTD4-induced bronchoconstriction with an ED50 of 0.6 mg/kg and anaphylactic death with an ED50 of 2.2 mg/kg and a half-life (t1/2) of 7 hours at 10 mg/kg. Additionally, RG-12525 inhibits antigen-induced bronchoconstriction with an ED50 of 0.6 mg/kg[1]. In the systemic anaphylaxis model, RG-12525 inhibits antigen-induced mortality with an ED50 (95% confidence interval) of 2.2 (0.8-6.4) mg/kg. Furthermore, RG-12525 protects against LTD4-induced bronchoconstriction in a model measuring changes in pulmonary function, with an ED50 of 0.6 (0.4-1.0) mg/kg[2].