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Drug-Target Interaction

Drug

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PubChem ID:4624
Structure:
Synonyms:
1,2,4-Benzenetriol, 5-(2-aminoethyl)-
1199-18-4
2,4,5-Trihydroxyphenethylamine
28094-15-7
28094-15-7 (hydrochloride)
4-13-00-02916 (Beilstein Handbook Reference)
5-(2-Aminoethyl)-1,2,4-benzenetriol
5-(2-aminoethyl)benzene-1,2,4-triol
6-HD
6-HYDROXYDOPAMINE
6-OHDA
636-00-0
636-00-0 (hydrobromide)
AC1L1IL1
BRN 2211011
BSPBio_003486
C8H11NO3
CCRIS 4342
CHEBI:317612
CHEMBL337702
D05294
DivK1c_000362
EINECS 214-842-3
Hydroxydopamine
IDI1_000362
KBio1_000362
KBio2_000789
KBio2_003357
KBio2_005925
KBio3_002706
KBioGR_000904
KBioSS_000789
LS-32261
NCGC00167769-01
NCGC00167769-02
NCI60_001890
NINDS_000362
Oxidopamina
Oxidopamina [INN-Spanish]
Oxidopamine
Oxidopamine (USAN/INN)
Oxidopamine [USAN:INN]
Oxidopaminum
Oxidopaminum [INN-Latin]
SPBio_001175
Spectrum2_001018
Spectrum3_001753
Spectrum4_000462
Spectrum_000309

Target

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Uniprot ID:CASP3_MOUSE
Synonyms:
Apopain
CASP-3
Caspase-3
CPP-32
Cysteine protease CPP32
LICE
SCA-1
SREBP cleavage activity 1
Yama protein
EC-Numbers:3.4.22.56
Organism:Mouse
Mus musculus
PDB IDs:-

Binding Affinities:

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

References:

17045926
A novel peptide inhibitor targeted to caspase-3 cleavage site of a proapoptotic kinase protein kinase C delta (PKCdelta) protects against dopaminergic neuronal degeneration in Parkinson's disease models.. Anumantha G Kanthasamy; Vellareddy Anantharam; Danhui Zhang; Calivarathan Latchoumycandane; Huajun Jin; Siddharth Kaul; Arthi Kanthasamy (2006) Free radical biology & medicine display abstract
Oxidative stress and apoptosis are considered common mediators of many neurodegenerative disorders including Parkinson's disease (PD). Recently, we identified that PKCdelta, a member of the novel PKC isoform family, is proteolytically activated by caspase-3 to induce apoptosis in experimental models of PD [Eur. J. Neurosci. 18 (6):1387-1401, 2003; Antioxid. Redox Signal. 5 (5):609-620, 2003]. Since caspase-3 cleaves PKCdelta between proline and aspartate residues at the cleavage site 324DIPD327 to activate the kinase, we developed an irreversible and competitive peptide inhibitor, Z-Asp(OMe)-Ile-Pro-Asp(OMe)-FMK (z-DIPD-fmk), to mimic the caspase-3 cleavage site of PKCdelta and tested its efficacy against oxidative stress-induced cell death in PD models. Cotreatment of z-DIPD-fmk with the parkinsonian toxins MPP(+) and 6-OHDA dose dependently attenuated cytotoxicity, caspase-3 activation, and DNA fragmentation in a mesencephalic dopaminergic neuronal cell model (N27 cells). However, z-DIPD-fmk treatment did not block MPP(+)-induced increases in caspase-9 enzyme activity. The z-DIPD-fmk peptide was much more potent (IC50 6 microM) than the most widely used and commercially available caspase-3 inhibitor z-DEVD-fmk (IC50 18 microM). Additionally, z-DIPD-fmk more effectively blocked PKCdelta cleavage and proteolytic activation than the cleavage of another caspase-3 substrate, poly(ADP-ribose) polymerase (PARP). Importantly, the peptide inhibitor z-DIPD-fmk completely rescued TH(+) neurons from MPP(+)- and 6-OHDA-induced toxicity in mouse primary mesencephalic cultures. Collectively, these results demonstrate that the PKCdelta cleavage site is a novel target for development of a neuroprotective therapeutic strategy for PD.