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Drug-Target Interaction

Drug

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PubChem ID:5315459
Structure:
Synonyms:
3''',8-Biflavone, 4',5,5'',7,7''-pentahydroxy-4'''-methoxy-
4'-Monomethylamentoflavone
521-32-4
8-[5-(5,7-dihydroxy-4-oxochromen-2-yl)-2-methoxyphenyl]-5,7-dihydroxy-2-(4
AC1NST1Z
Ambap3916
Ambap521-32-4
Bilobetin
CHEBI:449099
CHEMBL378188
CID5315459

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:

10588517
The effects of two new antagonists of secretory PLA2 on TNF, iNOS, and COX-2 expression in activated macrophages.. S H Baek; S S Yun; T K Kwon; J R Kim; H W Chang; J Y Kwak; J H Kim; K B Kwun (1999) Shock (Augusta, Ga.) display abstract
Phospholipase A2 (PLA2) regulates eicosanoid and platelet-activating factor production. It also plays an important role in the regulation of critical mediators in inflammatory diseases in which PLA2 activity is significantly enhanced during sepsis and multiple organ failure. Therefore, inhibitors of PLA2 activity offer themselves as target substances in the development of anti-inflammatory drugs. We identified 2 biflavonoids, bilobetin and ginkgetin, that can inhibit PLA2 activity. In experiments using 2-linol-[1-14C]PE as substrate both substances potently inhibited several kinds of type II 14-kDa PLA2 while inhibiting type I 14-kDa PLA2 to a lesser extent. We tested these PLA2 inhibitors for their ability to inhibit the production of tumor necrosis factor alpha (TNFalpha) and 2 enzymes, inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in an assay system using lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. In Raw264.7cells, bacterial LPS induced the production of COX-2 and iNOS proteins as well as TNFalpha. The inhibitors consistently inhibited the production of TNFalpha in a dose-dependent manner. Moreover, treatment of the macrophages with bilobetin and ginkgetin shut down the production of nitrite, one of the stable end products of NO released into the culture supernatant. The decrease in NO products was accompanied by a decrease in iNOS protein level as assessed by Western blot probed with specific anti-iNOS antibody. Both inhibitors also reduced the expression of COX-2 protein in the LPS-stimulated cells, which coincided with the reduction in iNOS protein. These results, therefore, suggest that these two sPLA2 inhibitors may be useful for inhibiting the production of inflammatory cytokine and NO production in inflammatory diseases.