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Chemical Compound Review

CbzValPheH     benzylN-[(1S)-2-methyl-1- [[(2S)-1-oxo-3...

Synonyms: Cbz-valpheh, Cbz-val-phe-H, Z-Val-Phe-CHO, Lopac-M-6690, CHEMBL286722, ...
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Disease relevance of Cbz-val-phe-H


High impact information on Cbz-val-phe-H


Biological context of Cbz-val-phe-H


Anatomical context of Cbz-val-phe-H

  • In this study, we assessed the protective effects of a calpain inhibitor (Cbz-Val-Phe-H) against hypoxic damage to the neocortex [1].
  • Trabecular myofilaments from normal hearts have a KD for Ca2+ of 6.27 +/- 0.06; I/R decreased the KD to 6.09 +/- 0.04; trabeculae from I/R hearts pre-treated with MDL-28170 have a KD of 6.28 +/- 0.04 [11].
  • Western blots showed that MDL 28170 suppressed 145/150 kDa subunits of alpha-spectrin breakdown products (SBDP) in cortex, hippocampus, thalamus, and striatum, and also 120-kDa subunit of SBDP in all regions except for striatum [12].
  • Neuropathological quantitative analysis of cell death showed that MDL 28170 significantly decreased the number of necrotic cells in all the examined regions except for cingular cortex, and the number of apoptotic cells in caudate putamen, parietal cortex, hippocampus CA1, and laterodorsal thalamus [12].
  • In contrast, only 23.6% of Purkinje cells were damaged in slices treated with Cbz-Val-Phe-H and AMPA [13].

Associations of Cbz-val-phe-H with other chemical compounds


Gene context of Cbz-val-phe-H

  • These data also suggest that calpain and related proteases, which are sensitive to MDL 28170, play an important role in the accumulation of secreted Abeta [19].
  • Pre-treatment of I/R hearts with MDL-28170 markedly diminishes PKM epsilon in reperfused hearts [11].
  • Western blot analysis of calpain substrates, GluR1, neuronal nitric oxide synthase (nNOS) and nonerythroid spectrin (fodrin), showed a time-dependent and MDL 28170-sensitive proteolysis of these proteins [7].
  • Calpain inhibitor III (MDL-28170) reduced caspase activation, suggesting that caspase activation was mediated by calpain [14].
  • The observations that three major cleavages within the transmembrane domain of APP, namely, the gamma-cleavage, -cleavage, and the newly identified zeta-cleavage, are involved in the generation of secreted Abeta40 and Abeta42 prompted us to determine how the calpain inhibitor III MDL 28170 influences these three cleavages and Abeta formation [19].

Analytical, diagnostic and therapeutic context of Cbz-val-phe-H


  1. Improved posthypoxic recovery of synaptic transmission in gerbil neocortical slices treated with a calpain inhibitor. Hiramatsu, K., Kassell, N.F., Lee, K.S. Stroke (1993) [Pubmed]
  2. Neuroprotection with a calpain inhibitor in a model of focal cerebral ischemia. Hong, S.C., Goto, Y., Lanzino, G., Soleau, S., Kassell, N.F., Lee, K.S. Stroke (1994) [Pubmed]
  3. The calpain inhibitor MDL 28170 prevents inflammation-induced neurofilament light chain breakdown in the spinal cord and reduces thermal hyperalgesia. Kunz, S., Niederberger, E., Ehnert, C., Coste, O., Pfenninger, A., Kruip, J., Wendrich, T.M., Schmidtko, A., Tegeder, I., Geisslinger, G. Pain (2004) [Pubmed]
  4. Calpain regulates enterocyte brush border actin assembly and pathogenic Escherichia coli-mediated effacement. Potter, D.A., Srirangam, A., Fiacco, K.A., Brocks, D., Hawes, J., Herndon, C., Maki, M., Acheson, D., Herman, I.M. J. Biol. Chem. (2003) [Pubmed]
  5. m-Calpain implication in cell cycle during muscle precursor cell activation. Raynaud, F., Carnac, G., Marcilhac, A., Benyamin, Y. Exp. Cell Res. (2004) [Pubmed]
  6. Endoplasmic reticulum Ca2+ depletion induces endothelial cell apoptosis independently of caspase-12. Nakano, T., Watanabe, H., Ozeki, M., Asai, M., Katoh, H., Satoh, H., Hayashi, H. Cardiovasc. Res. (2006) [Pubmed]
  7. Early calpain-mediated proteolysis following AMPA receptor activation compromises neuronal survival in cultured hippocampal neurons. Araújo, I.M., Verdasca, M.J., Leal, E.C., Bahr, B.A., Ambrósio, A.F., Carvalho, A.P., Carvalho, C.M. J. Neurochem. (2004) [Pubmed]
  8. beta-Amyloid (1-40)-induced apoptosis of cultured cortical neurones involves calpain-mediated cleavage of poly-ADP-ribose polymerase. Boland, B., Campbell, V. Neurobiol. Aging (2003) [Pubmed]
  9. Calpain inhibitors prevent neuronal cell death and ameliorate motor disturbances after compression-induced spinal cord injury in rats. Arataki, S., Tomizawa, K., Moriwaki, A., Nishida, K., Matsushita, M., Ozaki, T., Kunisada, T., Yoshida, A., Inoue, H., Matsui, H. J. Neurotrauma (2005) [Pubmed]
  10. Ischemia promotes calpain-mediated degradation of p120-catenin in SH-SY5Y cells. Ohno, H., Uemura, K., Shintani-Ishida, K., Nakamura, M., Inomata, M., Yoshida, K. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  11. MDL-28170, a membrane-permeant calpain inhibitor, attenuates stunning and PKC epsilon proteolysis in reperfused ferret hearts. Urthaler, F., Wolkowicz, P.E., Digerness, S.B., Harris, K.D., Walker, A.A. Cardiovasc. Res. (1997) [Pubmed]
  12. Calpain inhibitor MDL 28170 protects hypoxic-ischemic brain injury in neonatal rats by inhibition of both apoptosis and necrosis. Kawamura, M., Nakajima, W., Ishida, A., Ohmura, A., Miura, S., Takada, G. Brain Res. (2005) [Pubmed]
  13. Attenuation of AMPA-induced neurotoxicity by a calpain inhibitor. Caner, H., Collins, J.L., Harris, S.M., Kassell, N.F., Lee, K.S. Brain Res. (1993) [Pubmed]
  14. Calpain activates caspase-3 during UV-induced neuronal death but only calpain is necessary for death. McCollum, A.T., Nasr, P., Estus, S. J. Neurochem. (2002) [Pubmed]
  15. Calpain inhibitors improve myocardial dysfunction and inflammation induced by endotoxin in rats. Tissier, S., Lancel, S., Marechal, X., Mordon, S., Depontieu, F., Scherpereel, A., Chopin, C., Neviere, R. Shock (2004) [Pubmed]
  16. The induction of CYP1A1 by oltipraz is mediated through calcium-dependent-calpain. Dale, Y., Eltom, S.E. Toxicol. Lett. (2006) [Pubmed]
  17. Epimerization study of the L,L- and L,D-diastereoisomers of the calpain inhibitor MDL 28170 by capillary electrophoresis. Chen, T.M., Jones, H.K. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. (2004) [Pubmed]
  18. Ischaemic stroke: new frontiers. Prabhakar, S., Das, C.P. Neurology India. (1999) [Pubmed]
  19. Calpain inhibitor MDL28170 modulates Abeta formation by inhibiting the formation of intermediate Abeta46 and protecting Abeta from degradation. Dong, Y., Tan, J., Cui, M.Z., Zhao, G., Mao, G., Singh, N., Xu, X. FASEB J. (2006) [Pubmed]
  20. Postischemic treatment with calpain inhibitor MDL 28170 ameliorates brain damage in a gerbil model of global ischemia. Li, P.A., Howlett, W., He, Q.P., Miyashita, H., Siddiqui, M., Shuaib, A. Neurosci. Lett. (1998) [Pubmed]
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