FK706

FK706 is a potent, slow-binding and competitive inhibitor of human neutrophil elastase with an IC₅₀ of 83 nM and a K_i of 4.2 nM. FK706 also inhibits mouse neutrophil elastase and porcine pancreatic elastase with IC₅₀s of 22 nM and 100 nM, respectively, and has no inhibitory activity against other serine proteinases such as human pancreatic trypsin, human pancreatic α-chymotrypsin and human leukocyte cathepsin G. FK706 has anti-inflammatory effect^[1][2]. IC50 & Target: IC50: 83 nM (Human neutrophil elastase), 22 nM (Mouse neutrophil elastase) and 100 nM (Porcine pancreatic elastase)^[1];
Ki: 4.2 nM (Human neutrophil elastase)^[1] In Vitro: FK706 effectively inhibits the hydrolysis of bovine neck ligament elastin (2 mg/mL final concentration) by human neutrophil elastase (4 μg/mL final concentration) with an IC50 value of 230 nM^[1].
FK706 blocks the release of inflammatory chemokines, suppresses the expression of IL-8 and MCP-1 mRNA, and suppresses NF-κB activation. It seems possible that FK706 may directly blocks human lung fibroblasts activation of NF-κB, preventing expression of inflammatory chemokines during cigarette smoke–induced lung inflammation^[2]. In Vivo: FK706 (10-100 mg/kg; subcutaneous injection; for 1-6 hours; male C57BL mice) treatment significantly suppresses human neutrophil elastase (20 μg/paw)-induced paw edema in mice in a dose-dependent manner (47% inhibition at a dose of 100 mg/kg)^[1].