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

Drug-Target Interaction

Drug

show drug details
PubChem ID:444899
Structure:
Synonyms:
(14C)Arachidonic acid
(5Z,8Z,11Z,14Z)-5,8,11,14-icosatetraenoic acid
(5Z,8Z,11Z,14Z)-Eicosatetraenoic acid
(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoic acid
(5Z,8Z,11Z,14Z)-Icosatetraenoic acid
(5Z,8Z,11Z,14Z)icosa-5,8,11,14-tetraenoic acid
10931_FLUKA
10931_SIGMA
1adl
1gnj
1vyg
5,8,11,14-Eicosatetraenoic acid
5,8,11,14-Eicosatetraenoic acid, (all-Z)-
5,8,11,14-Eicosatetraenoic acid, labeled with carbon-14, (all-Z)-
5,8,11,14-Icosatetraenoic Acid
506-32-1
5Z,8Z,11Z,14Z-icosatetraenoic acid
93444-49-6
A0781
A3555_SIGMA
A3925_SIGMA
A9673_SIGMA
AA
AB1004494
AC-14348
AC1L9H30
ACD
AG-F-70356
AIDS-045704
AIDS045704
all-cis-5,8,11,14-eicosatetraenoic acid
ARA
Arachidonate
Arachidonic acid
ARACHIDONIC ACID (20:4 n-6)
Arachidonsaeure
BML3-B03
BRD-K03070961-001-02-8
BSPBio_001539
C00219
CHEBI:15843
CHEMBL15594
cis,cis,cis,cis-5,8,11,14-Eicosatetraenoic acid
cis,cis,cis,cis-5,8,11,14-Eicosatetraenoic acid;
cis-5,8,11,14-Eicosatetraenoic acid
cis-Delta(5,8,11,14)-eicosatetraenoic acid
D18DBC10-379C-4E78-9A50-8B791A2F4E68
Eicosa-5Z,8Z,11Z,14Z-tetraenoic acid
HMS1361M21
HMS1791M21
HMS1989M21
Icosa-5,8,11,14-tetraenoic acid
IDI1_034009
LMFA01030001
MLS001361328
MolPort-003-666-529
NCGC00094608-01
NCGC00094608-02
NCGC00094608-03
NCGC00094608-04
NCGC00094608-05
NCGC00094608-06
nchembio.129-comp13
nchembio.86-comp6
SMR000857374
Spectrum5_001910
ST069383
[1-14C]Arachidonic acid

Target

show target details
Uniprot ID:PGH1_MOUSE
Synonyms:
COX-1
Cyclooxygenase-1
PGH synthase 1
PGHS-1
PHS 1
Prostaglandin G/H synthase 1
Prostaglandin H2 synthase 1
Prostaglandin-endoperoxide synthase 1
EC-Numbers:1.14.99.1
Organism:Mouse
Mus musculus
PDB IDs:-

Binding Affinities:

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

References:

12925531
A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385.. Scott W Rowlinson; James R Kiefer; Jeffery J Prusakiewicz; Jennifer L Pawlitz; Kevin R Kozak; Amit S Kalgutkar; William C Stallings; Ravi G Kurumbail; Lawrence J Marnett (2003) The Journal of biological chemistry display abstract
A variety of drugs inhibit the conversion of arachidonic acid to prostaglandin G2 by the cyclooxygenase (COX) activity of prostaglandin endoperoxide synthases. Several modes of inhibitor binding in the COX active site have been described including ion pairing of carboxylic acid containing inhibitors with Arg-120 of COX-1 and COX-2 and insertion of arylsulfonamides and sulfones into the COX-2 side pocket. Recent crystallographic evidence suggests that Tyr-385 and Ser-530 chelate polar or negatively charged groups in arachidonic acid and aspirin. We tested the generality of this binding mode by analyzing the action of a series of COX inhibitors against site-directed mutants of COX-2 bearing changes in Arg-120, Tyr-355, Tyr-348, and Ser-530. Interestingly, diclofenac inhibition was unaffected by the mutation of Arg-120 to alanine but was dramatically attenuated by the S530A mutation. Determination of the crystal structure of a complex of diclofenac with murine COX-2 demonstrates that diclofenac binds to COX-2 in an inverted conformation with its carboxylate group hydrogen-bonded to Tyr-385 and Ser-530. This finding represents the first experimental demonstration that the carboxylate group of an acidic non-steroidal anti-inflammatory drug can bind to a COX enzyme in an orientation that precludes the formation of a salt bridge with Arg-120. Mutagenesis experiments suggest Ser-530 is also important in time-dependent inhibition by nimesulide and piroxicam.