Description
AM679 is a potent and selective FLAP inhibitor with IC50s of 2.2nM/0.6nM/154nM for FLAP binding/hLA/hWB respectively. IC50 value: 2.2nM/0.6nM/154nM(FLAP binding/hLA/hWB) [1] AM679 showed an improved CYP inhibition profile (IC50 3A4 = 16.7 lM, 2C9 = 3.7 lM, 2D6 >30 lM), no time dependent inhibition against CYP3A4 (0.003 min-1 vs 0.057 min-1 for troleandomycin control 10uM) and no CYP3A4 induction. AM679 has an excellent hWB IC50 potency of 154nM. Target: FLAP in vitro: AM679 showed excellent in vitro inhibition against FLAP. in vivo: AM679 was profiled in a rodent bronchoalveolar lavage (BAL) model to measure its ability to inhibit production of leukotrienes in vivo. 16 Oral administration of 39 (10mg/kg as the sodium carboxylate salt) 4 h prior to ionophore challenge reduced LTB4 and CysLT levels in the rodent lung lavage fluid by 98% and 87%, respectively, with corresponding average rodent plasma levels of 605nM (3 h post dose, rat blood LTB4 IC50 = 125nM)