Calpain inhibitor VI is an inhibitor of the calcium-dependent cysteine proteases u-calpain (calpain-1; IC50 = 7.5 nM) and m-calpain (calpain-2; IC50 = 78 nM). It also inhibits cathepsins B and L (IC50s = 15 and 1.6 nM, respectively). It is selective for these calpains and cathepsins over other cysteine and serine proteases, factor VIIa, factor Xa, trypsin, chymotrypsin, and proteasome. In an in vitro porcine model of cataract, calpain inhibitor VI decreases the degree of cataract by 40% when used at a concentration of 0.8 uM. It also prevents cataract formation induced by selenite in rats when administered at a dose of 100 mg/kg for 4 days. Calpain inhibitor VI improves functional outcome and reduces apoptotic cell death in a rat model of spinal cord injury.

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