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Drug-Target Interaction

Drug

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PubChem ID:4553
Structure:
Synonyms:
123653-11-2
AC1L1IF7
AC1Q20LP
AR-1K3665
Bio2_000472
Bio2_000952
BRD-K53364951-001-02-6
BSPBio_001264
C080955
C13H18N2O5S
CCRIS 8523
CHEBI:101699
CHEMBL7162
HMS1362P05
HMS1792P05
HMS1990P05
I14-10018
IDI1_002227
IN1319
KBio2_000604
KBio2_003172
KBio2_005740
KBio3_001067
KBio3_001068
KBioGR_000604
KBioSS_000604
LS-90104
Methanesulfonamide, N-(2-(cyclohexyloxy)-4-nitrophenyl)-
N-(2-Cyclohexyloxy-4-nitrophenyl)methanesulfonamide
N-[2-(Cyclohexyloxy)-4-nitrophenyl]methanesulfonamide
N194_SIGMA
NCGC00024892-01
NCGC00024892-02
NCGC00024892-03
nchembio.147-comp10
NS 398
NS-398
NS398
NS4
Tocris-0942
ZINC03791739

Target

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Uniprot ID:PGH1_HUMAN
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:Homo sapiens
Human
PDB IDs:-

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----
----
--3000-
--3300-
-->10000-
-->20000-
-->66000-
-->100000-

References:

11029586
Coordinate up- and down-regulation of glutathione-dependent prostaglandin E synthase and cyclooxygenase-2 in A549 cells. Inhibition by NS-398 and leukotriene C4.. S Thorén; P J Jakobsson (2000) European journal of biochemistry / FEBS display abstract
Recently, a microsomal protein with 38% sequence identity to microsomal glutathione S-transferase 1 was shown to constitute an inducible, glutathione-dependent prostaglandin E synthase (PGES). To investigate the relationship between cyclooxygenase and PGES, a time-course study on protein expression was performed in A549 cells after treatment with interleukin-1beta. The result demonstrated a tandem expression of cyclooxygenase-2 and PGES. The observed induction of PGES protein correlated with microsomal PGES activity. No comparable PGES activity was observed in the absence of glutathione or in the cytosolic fraction. In addition, tumour necrosis factor-alpha was found to induce PGES in these cells. Dexamethasone was found to completely suppress the effect of both cytokines on PGES induction. We also describe a quantitative method, based on RP-HPLC with UV detection for the measurements of PGES activity. This method was used to screen potential PGES inhibitors. Several nonsteroidal anti-inflammatory drugs, stable prostaglandin H2 analogues and cysteinyl leukotrienes were screened for inhibition of PGES activity. NS-398, sulindac sulfide and leukotriene C4 were all found to inhibit PGES activity with IC50 values of 20 microM, 80 microM and 5 microM, respectively. In conclusion, it appears that PGES and cyclooxygenase-2 are functionally coupled in A549 cells and that a required coordinate expression of these enzymes allows for efficient biosynthesis of prostaglandin E2.
16169124
Differential effects of COX inhibitors against beta-amyloid-induced neurotoxicity in human neuroblastoma cells.. P Ferrera; C Arias (2005) Neurochemistry international display abstract
Retrospective epidemiological studies have suggested that chronic treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) provides some degree of protection from Alzheimer's disease (AD). Although most NSAIDs inhibit the activity of cyclooxygenase (COX), the rate-limiting enzyme in the production of prostanoids from arachidonic acid (AA), the precise mechanism through which NSAIDs act upon AD pathology remains to be elucidated. Classical NSAIDs like indomethacin inhibit both the constitutive COX-1 and the inducible COX-2 enzymes. In the present work, we characterize the protective effect of the indomethacin on the neurotoxicity elicited by amyloid-beta protein (A beta, fragments 25-35 and 1-42) alone or in combination with AA added exogenously as well as its effects on COX-2 expression. We also compared the neuroprotective effects of indomethacin with the selective COX-1, COX-2 and 5-LOX inhibitors, SC-560, NS-398 and NDGA, respectively. Our results show that indomethacin protected from A beta and AA toxicity in naive and differentiated human neuroblastoma cells with more potency than SC-560 while, NS-398 only protected neurons from AA-mediated toxicity. Present results suggest that A beta toxicity can be reversed more efficiently by the non-selective COX inhibitor indomethacin suggesting its role in modulating the signal transduction pathway involved in the mechanism of A beta neurotoxicity.