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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:UROK_MOUSE
Synonyms:
U-plasminogen activator
uPA
Urokinase-type plasminogen activator
EC-Numbers:3.4.21.73
Organism:Mouse
Mus musculus
PDB IDs:-

Binding Affinities:

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

15325613
NS-398 inhibits tumor growth and liver metastasis of colon cancer through induction of apoptosis and suppression of the plasminogen activation system in a mouse model.. Masayasu Nishikawa; Philip P Stapleton; Tracy A Freeman; John P Gaughan; Takeaki Matsuda; John M Daly (2004) Journal of the American College of Surgeons display abstract
BACKGROUND: Cyclooxygenase-2 (COX-2) is overexpressed in colon cancers. The plasminogen activation (PA) system relates to cancer invasion and metastasis through the degradation of the extracellular matrix. COX-2 also relates to degradation of the extracellular matrix, but the relationship between COX-2 and the plasminogen activator system is unclear. STUDY DESIGN: In vivo: Colon 38 (G0) primary and (G5) metastatic cell lines were implanted in C57BL/6 mice treated with or without COX-2 inhibitor (NS-398). Animal survival and tumor growth were measured. On day 19, tumors were excised and tumor cell apoptosis measured. For metastasis, G5 cells were injected into the spleen, and, after 23 days, liver metastasis was determined. In vitro: G0 or G5 cells were treated with NS-398. Supernatant prostaglandin E2 and mRNA expressions of COX-2, vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (u-PA), u-PA receptor, plasminogen activator inhibitor type-1 (PAI-1), and PAI-2 were measured. Tumor cell proliferation was also determined. RESULTS: In vivo: Mean survival of NS-398-treated animals was higher than controls for both G5 and G0 (G5: p < 0.003, G0: p < 0.02). G5 tumors grew faster than G0 tumors (p < 0.001) and NS-398 significantly inhibited tumor growth (p < 0.001), induced tumor cell apoptosis (p < 0.001), and significantly reduced metastasis (p < 0.003) in G5 animals. In vitro: PGE(2) production was higher in G5 than G0 cells (p < 0.001); NS-398 significantly reduced prostaglandin E(2) levels in G5 cells (p < 0.001). mRNA expression of COX-2, vascular endothelial growth factor, and u-PA receptor was higher in G5 than G0 cells, and NS-398 significantly inhibited u-PA mRNA expression in G5 cells. NS-398 significantly reduced proliferation in G5 cells (p < 0.05). CONCLUSIONS: COX-2 inhibition significantly decreases tumor growth in this model by inducing apoptosis and blocking u-PA production in G5 colon cancer cells, which is associated with significant inhibition of liver metastases.