Home
Drugs
Targets
Pathways
Ontologies
Cyp450s
Adv.search
Help/FAQ

Drug-Target Interaction

Drug

show drug details
PubChem ID:198756
Structure:
Synonyms:
(-)-(R)-2-(4-((Chroman-2-ylmethyl)amino)butyl)-1,1-dioxo-1,2-benzisothiazo
(-)-(R)-2-(4-((Chroman-2-ylmethyl)amino)butyl)-1,1-dioxo-1,2-benzisothiazol-3(2H)-one HCl
1,2-Benzisothiazol-3(2H)-one, 2-(4-(((3,4-dihydro-2H-1-benzopyran-2-yl)methyl)amino)butyl)-, 1,1-dioxide, monohydrochloride, (-)-
144980-77-8
Bay x 3702
Bay-x-3702
Branosyn
LS-33613
Repinotan hydrochloride
X-3702

Target

show target details
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:

12676358
The G protein-coupled 5-HT1A receptor causes suppression of caspase-3 through MAPK and protein kinase Calpha.. Tatyana Adayev; Indrani Ray; Rachna Sondhi; Tomasz Sobocki; Probal Banerjee (2003) Biochimica et biophysica acta display abstract
The 5-HT(1A) agonist 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) causes inhibition of caspase-3 and apoptosis via the extracellular signal-regulated kinases (ERK1/2) in hippocampal HN2-5 cells. Two 5-HT(1A) agonists, Repinotan hydrochloride (BAY x 3702) and 8-OH-DPAT, block caspase-3 activation and apoptosis caused by anoxia/reoxygenation and H(2)O(2) treatment. This is reversed upon transient expression of dominant negative Ras (N17Ras) and Raf-1 (Raf301), confirming the involvement of Ras and Raf-1 in this 5-HT(1A)-R-->ERK1/2-->caspase-3 pathway. A selective inhibitor of phospholipase Cbeta (PLCbeta) (U73122) but not a general protein kinase C (PKC) inhibitor (GFX) reversed the 5-HT(1A)-R-mediated ERK1/2 stimulation. However, both GFX and the PKCalpha and PKCbeta(1) inhibitor G6976 reversed the ERK1/2-mediated inhibition of caspase-3. ERK-dependent activation of only PKCalpha was observed in immunoprecipitates obtained from 5-HT(1A) agonist-treated HN2-5 cells. Finally, transient expression of kinase-negative PKCalpha eliminated the 8-OH-DPAT-evoked block on the H(2)O(2)-triggered caspase-3 stimulation, establishing PKCalpha as a link between ERK and caspase-3 (5-HT(1A)-R-->PLC-->ERK1/2-->PKCalpha-->caspase-3). Our results elucidate a novel yet general, neuroprotective pathway through which G protein-coupled receptors could cause inhibition of effector caspases, such as caspase-3.