MX1013 is a dipeptide pan-caspase inhibitor that inhibits caspase-1 (IC50 = 20 nM), caspase-3 (IC50 = 30 nM), and caspase-6, -7, -8, and -9 (IC50s = 5-18 nM).1 It is selective for caspases over calpain I, cathepsin B, cathepsin D, renin, thrombin, and Factor Xa (IC50s = >10 μM). MX1013 (0.05 μM) inhibits anti-Fas antibody-induced caspase-3 processing and poly(ADP)ribose polymerase (PARP) cleavage in Jurkat cells, indicating inhibition of apoptosis. It increases survival in a mouse model of anti-Fas antibody-induced liver failure when administered at doses of greater than or equal to 0.25 mg/kg. MX1013 reduces infarct size in rat models of acute myocardial infarction-reperfusion or transient focal brain ischemia-reperfusion injury when administered intravenously as a 20 mg/kg bolus dose followed by a 5 mg/kg per hour infusion.
References
1. Yang, W., Guastella, J., Huang, J.-C., et al. MX1013, a dipeptide caspase inhibitor with potent in vivo antiapoptotic activity. Br. J. Pharmacol. 140(2), 402-412 (2003).