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

Drug-Target Interaction

Drug

show drug details
PubChem ID:151166
Structure:
Synonyms:
2-((2-Chloro-6-fluorophenyl)amino)-5-methylbenzeneacetic acid
2-((2-Chloro-6-fluorophenyl)amino)-5-methylphenyl)acetic acid
2-(2-((2-chloro-6-fluoro-phenyl)amino)-5-methyl-phenyl)acetic acid
2-[2-(2-chloro-6-fluoroanilino)-5-methylphenyl]acetic acid
2-[2-[(2-chloro-6-fluorophenyl)amino]-5-methylphenyl]acetic acid
220991-20-8
AC-1738
AC1L45SO
Benzeneacetic acid, 2-((2-chloro-6-fluorophenyl)amino)-5-methyl-
C473384
CHEBI:524824
CHEMBL404108
COX 189
COX-189
COX189
D03714
DB01283
HMS3264F19
I06-0368
Joicela
LS-185762
LS-187022
LS-187647
Lumiracoxib
Lumiracoxib (USAN/INN)
Lumiracoxib [USAN:INN]
NCGC00181795-01
Prexige
Prexige (Novartis)
STOCK6S-73581
UNII-V91T9204HU
ATC-Codes:

Target

show target details
Uniprot ID:PGH2_SHEEP
Synonyms:
COX-2
Cyclooxygenase-2
PGH synthase 2
PGHS-2
PHS II
Prostaglandin G/H synthase 2
Prostaglandin H2 synthase 2
Prostaglandin-endoperoxide synthase 2
EC-Numbers:1.14.99.1
Organism:Ovis aries
Sheep
PDB IDs:-

Binding Affinities:

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

References:

17434872
Molecular determinants for the selective inhibition of cyclooxygenase-2 by lumiracoxib.. Anna L Blobaum; Lawrence J Marnett (2007) The Journal of biological chemistry display abstract
Lumiracoxib is the first example of a marketed COX-2 inhibitor of the arylacetic acid class, and it is reported to be the most selective COXIB in vivo. However, the molecular basis of its COX-2 inhibition has not been completely defined. Using standard assays, lumiracoxib was found to be a poor inhibitor of purified ovine COX-1 and a relatively weak inhibitor of purified human COX-2. The extent of COX-2 inhibition plateaued at around 50% and suggested that the inhibitor may be reversibly bound to the enzyme. Kinetic studies with lumiracoxib demonstrated that it was a time-dependent and slowly reversible inhibitor of human COX-2 that exhibited at least two binding steps during inhibition. Derivatives of lumiracoxib were synthesized with or without the methyl group on the phenylacetic acid ring and with various substitutions on the lower aniline ring. Inhibition studies demonstrated that the methyl group on the phenylacetic acid ring is required for COX-2 selectivity. The chemical identity and position of the substituents on the lower aniline ring were important in determining the potency and extent of COX inhibition as well as COX-2 selectivity. Mutation of Ser-530 to Ala or Val-349 to Ala or Leu abolished the potent inhibition observed with wild-type human COX-2 and key lumiracoxib analogs. Interestingly, a Val-349 to Ile mutant was inhibited with equal potency to human COX-2 with 2,6-dichloro-, 2,6-dimethyl-, or 2-chloro-6-methyl-substituted inhibitors and, in the case of lumiracoxib, actually showed an increase in potency. Taken together with a recent crystal structure of a lumiracoxib-COX-2 complex, the kinetic analyses presented herein of the inhibition of mutant COX-2s by lumiracoxib allows the definition of the molecular basis of COX-2 inhibition.