Biochemicals & reagents
1) Chard et al. (1995), Capsaicin-induced neurotoxicity in cultured dorsal root ganglion neurons: involvement of calcium-activated proteases; Neuroscience, 65 1099 2) Li et al. (1998), Postischemic treatment with calpain inhibitor MDL28170 ameliorates brain damage in a gerbil model of global ischemia; Neurosci. Lett., 247 17 3) Thompson et al. (2010), A pharmacological analysis of the neuroprotective efficacy of the brain- and cell-permeable calpain inhibitor MDL-28170 in the mouse controlled cortical impact traumatic brain injury model; J. Neurotrauma, 27 2233 4) Chatterjee et al. (1998), D-amino acid containing, high-affinity inhibitors of recombinant human calpain I; J. Med. Chem., 41 2663
MDL-28170 is a potent and selective cell permeable calpain inhibitor which inhibits the oxidative damage-induced apoptosis in PC12 cells and capsaicin-induced apoptosis in dorsal root ganglion neurons (1). This compound also penetrates the blood-brain barrier and inhibits brain cysteine protease activity after systemic administration, ameliorating brain damage in a gerbil model of global ischemia (2) and displays neuroprotective effects in neurotrama rodent models (3). in isolated enzyme assays Calpain I has a Ki = 8 nM and Cathepsin B has a Ki = 24 nM with an IC50 = 0.3 µM in intact cell assay (4).