BI-4394

BI-4394 (MMP13-IN-3) is a potent, selective, and orally active MMP-13 inhibitor (IC₅₀=1 nM^[1]) for the potential treatment of osteoarthritis^[2]. BI-4394 is >1000 selective over other MMPs^[1]. In Vitro:BI-4394 (Compound 15) is potent in a full-length MMP-13 collagen degradation assay (11 nM) and is able to inhibit degradation of bovine nasal cartilage with an IC₅₀ of 31 nM. BI-4394 inhibits MMP-2, MMP-9, MMP-10 and MMP-14 with IC₅₀s of 18, 8.9, 16 and 8.3 μM, respectively^[1]. In Vivo:When dosed orally at 10 mg/kg or i.v. 1 mg/kg, BI-4394 (Compound 15) reaches micromolar plasma levels (AUC=1109±64 nM h/mL), displays modest clearance (CL=34 mL/min/kg), and shows acceptable bioavailability (39%). The V_ss is quite low at 0.26 mL/mi/kg rat pharmacokinetic profile. BI-4394 has short terminal elimination half-life (t_1/2=0.47 h for rat (1 mg/kg, i.v.) and rat (10 mg/kg, orally), respectively)^[1].