产品描述: | BI-4394 (MMP13-IN-3) 是一种有效的选择性口服活性 MMP-13 抑制剂(IC50=1 nM)的潜在治疗骨关节炎.BI-4394 比其他 MMP 具有 >1000 选择性 |
靶点: |
MMP-13:1 nM (IC50);MMP-14:8.3 μM (IC50);MMP-9:8.9 μM (IC50);MMP-10:16 μM (IC50);MMP-2:18 μM (IC50);MMP |
体外研究: |
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. |
体内研究: |
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). Animal Model:Srapgue Dally Rats Dosage:10 mg/kg (oral gavage); 1 mg/kg (i.v.) Administration:Dosed orally (10 mg/kg); i.v. (1 mg/kg)(Pharmacokinetic Analysis)Result:T1/2=0.47 h for rat (1 mg/kg, i.v.) and rat (10 mg/kg, orally) , respectively. |
参考文献: |
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. |
溶解性: |
Soluble in DMSO |
保存条件: |
-20℃ |
配置溶液浓度参考: |
|
1mg |
5mg |
10mg |
1 mM |
2.24 ml |
11.199 ml |
22.398 ml |
5 mM |
0.448 ml |
2.24 ml |
4.48 ml |
10 mM |
0.224 ml |
1.12 ml |
2.24 ml |
50 mM |
0.045 ml |
0.224 ml |
0.448 ml |
|
注意: |
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