MMP13-IN-3 是一种有效的，具有口服活性的选择性 MMP-13 抑制剂，IC50 为 1 nM，比作用于其他 MMP 的选择性高 1000倍多。MMP13-IN-3 有潜力用于骨关节炎的研究。
货号:ajcx35454
CAS:1222173-37-6
分子式:C24H22N4O5
分子量：446.46
溶解度:DMSO : 100 mg/mL (223.98 mM; ultrasonic and warming and heat to 60°C)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

MMP13-IN-3 is a potent, selective, and orally active MMP-13 inhibitor (IC50=1 nM[1]) for the potential treatment of osteoarthritis[2]. MMP13-IN-3 is >1000 selective over other MMPs[1].

MMP13-IN-3 (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. MMP13-IN-3 inhibits MMP-2, MMP-9, MMP-10 and MMP-14 with IC50s of 18, 8.9, 16 and 8.3 μM, respectively[1].

When dosed orally at 10 mg/kg or i.v. 1 mg/kg, MMP13-IN-3 (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 Vss is quite low at 0.26 mL/mi/kg rat pharmacokinetic profile. MMP13-IN-3 has short terminal elimination half-life (t1/2=0.47 h for rat (1 mg/kg, i.v.) and rat (10 mg/kg, orally), respectively)[1].

[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.
[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.