BI-4394  (Synonyms: MMP13-IN-3)

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].

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

446.46

C₂₄H₂₂N₄O₅

1222173-37-6

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• [1]. Taylor SJ, et al. Fragment-based discovery of indole inhibitors of matrix metalloproteinase-13. J Med Chem. 2011 Dec 8;54(23):8174-87.  [Content Brief]

  [2]. Ruminski PG, et al. Discovery of N-(4-Fluoro-3-methoxybenzyl)-6-(2-(((2S,5R)-5-(hydroxymethyl)-1,4-dioxan-2-yl)methyl)-2H-tetrazol-5-yl)-2-methylpyrimidine-4-carboxamide. A Highly Selective and Orally Bioavailable Matrix Metalloproteinase-13 Inhibitor for the Potential Treatment of Osteoarthritis. J Med Chem. 2016 Jan 14;59(1):313-27.  [Content Brief]