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.1?It 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?Displays neuroprotective effects in neurotrauma rodent models.3?Calpain I Ki?= 8 nM; Cathepsin B Ki?= 24 nM in isolated enzyme assays. IC50?= 0.3 μM in intact cell assay.4
Uses
Inhibits calpain proteolysis
Uses
MDL 28170 acts as a caplain inhibitor reducing hypoxia in ischemic-retinopathy, and various other neuroprotective effects.
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) 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
