Disease relevance of Cbz-val-phe-H

• In contrast, synaptic recovery after a fixed period of hypoxia (15 minutes) was significantly improved in the Cbz-Val-Phe-H-treated slices (P < .01) [1].
• RESULTS: Rats treated with Cbz-Val-Phe-H exhibited significantly smaller volumes of cerebral infarction than saline-treated or vehicle-treated control animals [2].
• Intravenous injections of cumulative doses of 30 mg/kg or 60 mg/kg of Cbz-Val-Phe-H were effective in reducing infarction, edema, and calcium-activated proteolysis [2].
• The calpain inhibitor MDL 28170 prevents inflammation-induced neurofilament light chain breakdown in the spinal cord and reduces thermal hyperalgesia [3].
• Nociception induced breakdown of NFL in the spinal cord and dorsal root ganglias was prevented by pretreatment of the animals with a single dose of the specific inhibitor of the protease calpain (MDL-28170) which has been shown to be the primary protease involved in neurofilament degradation in neurodegenerative diseases [3].

High impact information on Cbz-val-phe-H

• Calpain inhibitors ZLLYCHN2, MDL 28170, and PD 150606 block BB assembly and ezrin recruitment to the BB [4].
• To determine the implication of m-calpain during the cell cycle progression, quiescent myoblasts were forced to re-enter the cell cycle in the presence or not of the specific calpain inhibitor MDL 28170 [5].
• METHODS: Twenty-five male Sprague-Dawley rats were divided into four groups: a saline-treated group, a vehicle-treated group, and two calpain inhibitor-treated groups (Cbz-Val-Phe-H; 30-mg/kg and 60-mg/kg cumulative doses) [2].
• A non-selective caspase inhibitor, z-VAD.fmk (100 microM), inhibited apoptosis and cleavage of caspase-12 stimulated by thapsigargin, while a calpain inhibitor, MDL 28170 (120 microM), inhibited caspase-12 cleavage but not apoptosis [6].
• At 1 h after treatment, we could already observe significantly increased calpain activity, which was prevented by MDL 28170 and NBQX [7].

Biological context of Cbz-val-phe-H

• Use of the cell-permeable calpain inhibitor, MDL 28170, has identified cleavage of the DNA-repair enzyme, poly-ADP-ribose polymerase, and DNA fragmentation as downstream consequences of calpain activation [8].
• We conducted a study to determine whether calpain mediates neuronal cell death in the motor neurons of the spinal cord after SCI, and whether postinjury administration of the calpain inhibitors N-acetyl- Leu-Leu-Met-CHO (ALLM) and calpain inhibitor III (CI III) (MDL28170) reduces the motor disturbances in rats with a model of SCI [9].
• Calpain inhibitors Cbz-Val-Phe-H (MDL28170, 20muM) and N-acetyl-leucyl-leucyl-norleucinal (ALLN, 20muM) increased the levels of dephosphorylated p120-catenin, aggregation, and cell survival as detected by reduced LDH release in ischemic cells [10].

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

• Calpain contributed to neuronal death, as indicated by strong neuroprotection provided by calpain inhibitor III, calpeptin, or Ca2+-free medium [14].
• Leupeptin and calpain inhibitor III reduced plasma TNF-alpha levels in endotoxin-treated rats [15].
• Treatment of cells with calpain specific inhibitor MDL 28170 completely blocked the oltipraz-induced nuclear translocation of AhR and subsequent CYP1A1 expression [16].
• This report describes a capillary electrophoresis (CE) method that uses sodium dodecyl sulfate (SDS) micellar electrokinetic conditions for the separation of the L,L- and L,D-diastereoisomers of MDL 28170 [17].
• Various other drugs e.g. aptiganel hydrochloride, MDL 28170, 'basic fibroblast growth factor' and 'superoxide dismutase' are at an experimental stage [18].

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

• The results show that the calpain inhibitor, MDL 28170, protects against cortical neuronal damage even if the treatment is delayed until 3 h after reperfusion [20].
• This experiment was initiated to determine if the calpain inhibitor, MDL 28170 could, by these actions, reduce neuronal damage in an animal model of global cerebral ischemia in the gerbil [20].
• With the use of a cell culture system, our data demonstrate that 1) at either high concentrations, or at a low range of concentrations, at early time points, MDL 28170 inhibits the formation of secreted Abeta40 and Abeta42 [19].

References