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Drug-Target Interaction

Drug

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PubChem ID:73364
Structure:
Synonyms:
117591-20-5
Benzyl N-[(1S)-3-methyl-1-[[(2S)-1-oxohexan-2-yl]carbamoyl]butyl]carbamate
Benzylcarbonyl-leu-nleu-H
Bio2_000238
Bio2_000718
BSPBio_001518
C11256
C20H30N2O4
Calpeptin
Carbamic acid, (1-(((1-formylpentyl)amino)carbonyl)-3-methylbutyl)-,
Carbamic acid, (1-(((1-formylpentyl)amino)carbonyl)-3-methylbutyl)-, phenylemthyl ester, (S-(R*,R*))-
Carbamic acid, (1-(((1-formylpentyl)amino)carbonyl)-3-methylbutyl)-, phenylmethyl ester, (S-(R*,R*))-
CPD0-1359
IDI1_033988
KBio2_000238
KBio2_002806
KBio2_005374
KBio3_000475
KBio3_000476
KBioGR_000238
KBioSS_000238
LS-172355
N-Cbz-leu-nleu-al
n2-[(benzyloxy)carbonyl]-n-[(2s)-1-oxohexan-2-yl]-l-leucinamide
NCGC00024594-01
NCGC00163432-01
NCGC00163432-02
nchembio.79-comp26
Tocris-0448
ZINC03871838

Target

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Uniprot ID:MK03_HUMAN
Synonyms:
ERK-1
ERT2
Extracellular signal-regulated kinase 1
Insulin-stimulated MAP2 kinase
MAP kinase 1
MAPK 1
Microtubule-associated protein 2 kinase
Mitogen-activated protein kinase 3
p44-ERK1
p44-MAPK
EC-Numbers:2.7.11.24
Organism:Homo sapiens
Human
PDB IDs:2ZOQ
Structure:
2ZOQ

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

15331404
Calpain mediates calcium-induced activation of the erk1,2 MAPK pathway and cytoskeletal phosphorylation in neurons: relevance to Alzheimer's disease.. Veeranna; Takahide Kaji; Barry Boland; Tatjana Odrljin; Panaiyur Mohan; Balapal S Basavarajappa; Corrinne Peterhoff; Anne Cataldo; Anna Rudnicki; Niranjana Amin; Bing Sheng Li; Harish C Pant; Basalingappa L Hungund; Ottavio Arancio; Ralph A Nixon (2004) The American journal of pathology display abstract
Aberrant phosphorylation of the neuronal cytoskeleton is an early pathological event in Alzheimer's disease (AD), but the underlying mechanisms are unclear. Here, we demonstrate in the brains of AD patients that neurofilament hyperphosphorylation in neocortical pyramidal neurons is accompanied by activation of both Erk1,2 and calpain. Using immunochemistry, Western blot analysis, and kinase activity measurements, we show in primary hippocampal and cerebellar granule (CG) neurons that calcium influx activates calpain and Erk1,2 and increases neurofilament phosphorylation on carboxy terminal polypeptide sites known to be modulated by Erk1,2 and to be altered in AD. Blocking Erk1,2 activity either with antisense oligonucleotides to Erk1,2 mRNA sequences or by specifically inhibiting its upstream activating kinase MEK1,2 markedly reduced neurofilament phosphorylation. Calpeptin, a cell-permeable calpain inhibitor, blocked both Erk1,2 activation and neurofilament hyperphosphorylation at concentrations that inhibit calpain-mediated cleavage of brain spectrin. By contrast, inhibiting Erk1,2 with U-0126, a specific inhibitor of Mek1,2, had no appreciable effect on ionomycin-induced calpain activation. These findings demonstrate that, under conditions of calcium injury in neurons, calpains are upstream activators of Erk1,2 signaling and are likely to mediate in part the hyperphosphorylation of neurofilaments and tau seen at early stages of AD as well as the neuron survival-related functions of the MAP kinase pathway.