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

Drug-Target Interaction

Drug

show drug details
PubChem ID:5472495
Structure:
Synonyms:
(Z)-5-Fluoro-2-methyl-1[p-(methylsulfonyl)benzylidene]indene-3-acetic Acid
1H-Indene-3-acetic acid, 5-fluoro-2-methy
1H-Indene-3-acetic acid, 5-fluoro-2-methy l-1-((4-(methylsulfonyl)phenyl)methylene)-
1H-Indene-3-acetic acid, 5-fluoro-2-methy l-1-((4-(methylsulfonyl)phenyl)methylene)-, (Z)-
1H-Indene-3-acetic acid, 5-fluoro-2-methyl-1-((4-(methylsulfonyl)phenyl)methylene)-, (1Z)-
5-Fluoro-2-methy l-1-((4-(methylsulfonyl)phenyl)methylene)-1H-indene-3-acetic acid
5-Fluoro-2-methyl-1-((Z)-p-(methylsulfonyl)benzylidene)indene-3-acetic acid
59864-04-9
59973-80-7
Aptosyn
C20H17FO4S
CCRIS 7242
cis-5-Fluoro-2-methyl-1-(p-methylsulfonylbenzylidenyl)indene-3-acetic acid
CP 248
CP248
Curator_000028
EU-0101115
Exisulind
FGN 1
FGN-1
Lopac-S-1438
Lopac0_001115
LS-176044
LS-176053
NCGC00015928-01
NCGC00094385-01
NCGC00162346-01
NSC719619
Prevatec
Sulindac sulfone
sulindac sulfone, (Z)-isomer
[(1Z)-5-fluoro-2-methyl-1-{[4-(methylsulfonyl)phenyl]methylidene}-1H-inden-3-yl]acetic acid

Target

show target details
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:

11245463
Inhibition of extracellular signal-regulated kinase 1/2 phosphorylation and induction of apoptosis by sulindac metabolites.. P L Rice; R J Goldberg; E C Ray; L J Driggers; D J Ahnen (2001) Cancer research display abstract
Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and sulindac is associated with a decreased mortality from colorectal cancer. Sulindac causes regression of precancerous adenomatous polyps and inhibits the growth of cultured colon cell lines. Whereas induction of apoptotic cell death is thought to account for the growth inhibitory effect of sulindac, less is known about its biochemical mechanism(s) of action. Sulindac is metabolized in vivo to sulfide and sulfone derivatives. Both the sulfide and sulfone metabolites of sulindac as well as more potent cyclic GMP-dependent phosphodiesterase inhibitors were shown to cause inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation at doses (40-600 microM) and times (1-5 days) consistent with the induction of apoptosis by the drugs. Treatment of HCT116 human colon cancer cells with the specific mitogen-activated protein kinase kinase, U0126 (5-50 microM) resulted in a time- and dose-dependent inhibition of ERK1/2 phosphorylation, and induction of apoptosis. U0126 treatment (20 microM) increased basal apoptosis, and potentiated the apoptotic effect of sulindac sulfide and sulindac sulfone. These results suggest that the inhibition of ERK1/2 phosphorylation is responsible for at least part of the induction of programmed cell death by sulindac metabolites. Inhibition of ERK1/2 activity may, therefore, be a useful biochemical target for the development of chemopreventive and chemotherapeutic drugs for human colon cancer.