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Drug-Target Interaction

Drug

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PubChem ID:119418
Structure:
Synonyms:
(4S)-4,5,6,7,8,9-Hexahydro-11,13-dihydroxy-4-methyl-2H-3-benzoxacyclododec
(4S)-4,5,6,7,8,9-Hexahydro-11,13-dihydroxy-4-methyl-2H-3-benzoxacyclododecin-2,10(1H)-dione
10140-70-2
2H-3-Benzoxacyclododecin-2,10(1H)-dione, 4,5,6,7,8,9-hexahydro-11,13-dihydroxy-4-methyl-, (S)- (9CI)
AC1L3OS5
AC1Q6M97
Ambotz10140-70-2
AR-1I2772
CHEMBL478770
CID119418
Curvularin
NSC 166071
ZINC01649222

Target

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Uniprot ID:NOS3_HUMAN
Synonyms:
cNOS
Constitutive NOS
EC-NOS
Endothelial NOS
eNOS
Nitric oxide synthase, endothelial
NOS type III
NOSIII
EC-Numbers:1.14.13.39
Organism:Homo sapiens
Human
PDB IDs:1M9J 1M9K 1M9M 1M9Q 1M9R 3EAH 3NOS
Structure:
3NOS

Binding Affinities:

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

References:

12527810
Sporogen, S14-95, and S-curvularin, three inhibitors of human inducible nitric-oxide synthase expression isolated from fungi.. Ying Yao; Michael Hausding; Gerhard Erkel; Timm Anke; Ulrich F÷rstermann; Hartmut Kleinert (2003) Molecular pharmacology display abstract
The induction of human inducible nitric-oxide synthase (iNOS) expression depends (among other factors) on activation of the signal transducer and activator of transcription 1 (STAT1) pathway. Therefore, the STAT1 pathway may be an appropriate target for the development of inhibitors of iNOS expression. HeLa S3 cells transiently transfected with a gamma-activated site (GAS)/interferon-stimulated response element-driven reporter gene construct were used as the primary screening system. Using this system, three novel inhibitors of interferon-gamma-dependent gene expression, namely, sporogen, S14-95, and S-curvularin, were isolated from different Penicillium species. These three compounds also inhibited cytokine-induced, GAS-dependent reporter gene expression in stably transfected human A549/8-pGASLuc cells, confirming the data obtained with the above-mentioned screening system. Furthermore, in A549/8 cells, sporogen, S14-95, and S-curvularin inhibited cytokine-induced activity of the human iNOS promoter [a 16-kilobase (kb) fragment in stably transfected A549/8-pNOS2(16)Luc cells], cytokine-induced iNOS mRNA expression, and cytokine-induced nitric oxide (NO) production in a concentration-dependent manner. The proliferation of A549/8 cells, and the activity of the human eNOS promoter (a 3.5-kb fragment in stably transfected ECV-pNOS III-Hu-3500-Luc cells), were only influenced marginally by the three compounds. Sporogen, S14-95, and S-curvularin also inhibited cytokine-induced activation of STAT1alpha in A549/8 cells. In conclusion, sporogen, S14-95, and S-curvularin represent new transcriptionally based inhibitors of iNOS-dependent NO production, acting on the Janus tyrosine kinase-STAT pathway. These compounds may represent lead structures for the development of drugs inhibiting iNOS-dependent overproduction of NO in pathophysiological situations.