Description
MDL-28170 (88191-84-8) is a potent and selective cell permeable calpain inhibitor. Inhibits oxidative damage-induced apoptosis in PC12 cells and capsaicin-induced apoptosis in dorsal root ganglion neurons.1It penetrates the blood-brain barrier and inhibits brain cysteine protease activity after systemic administration, ameliorating brain damage in a gerbil model of global ischemia.2Displays neuroprotective effects in neurotrauma rodent models.3Calpain I Ki= 8 nM; Cathepsin B Ki= 24 nM in isolated enzyme assays. IC50= 0.3 μM in intact cell assay.4
Uses
MDL 28170 acts as a caplain inhibitor reducing hypoxia in ischemic-retinopathy, and various other neuroprotective effects.
Uses
Inhibits calpain proteolysis
Definition
ChEBI: A dipeptide resulting from the formal condensation of the carboxy group of N-benzyloxycarbonyl-L-valine with the amino group of L-phenylalanine aldehyde. It is a potent cell-permeable inhibitor of calpai
I and II, and is also a gamma-secretase inhibitor.
General Description
A potent, cell-permeable inhibitor of calpain I and II (K
i = 8 nM) that also reduces capsaicin-mediated cell death in cultured dorsal root ganglion. Reported to block A23187-induced suppression of neurite outgrowth in isolated hippocampal pyramidal neurons. Exhibits neuroprotective effects against glutamate-induced toxicity.
Biological Activity
Potent, selective inhibitor of calpain and cathepsin B (K i values are 10 and 25 nM respectively) that does not inhibit trypsin-like serine proteases. Rapidly penetrates the blood-brain barrier following systemic administration and displays neuroprotective effects in vivo .
Biochem/physiol Actions
Cell permeable: yes
References
[1] P.S. CHARD. Capsaicin-induced neurotoxicity in cultured dorsal root ganglion neurons: Involvement of calcium-activated proteases[J]. Neuroscience, 1995, 65 4: Pages 1099-1108. DOI:
10.1016/0306-4522(94)00548-j[2] PING-AN LI . Postischemic treatment with calpain inhibitor MDL 28170 ameliorates brain damage in a gerbil model of global ischemia[J]. Neuroscience Letters, 1998, 247 1: Pages 17-20. DOI:
10.1016/s0304-3940(98)00266-3[3] STEPHANIE N THOMPSON. 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]. Journal of neurotrauma, 2010, 27 12: 2233-2243. DOI:
10.1089/neu.2010.1474[4] SANKAR CHATTERJEE. d-Amino Acid Containing, High-Affinity Inhibitors of Recombinant Human Calpain I†[J]. Journal of Medicinal Chemistry, 1998, 41 15: 2663-2666. DOI:
10.1021/jm980035y
