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Drug-Target Interaction

Drug

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PubChem ID:250
Structure:
Synonyms:
3-[2-[[3-(2-carboxyethyl)-5-[(3-ethenyl-4-methyl-5-oxopyrrol-2-ylidene)met
AC1L18TG
Bilirubin
CID250
DivK1c_006697
KBio1_001641
KBio2_001685
KBio2_004253
KBio2_006821
KBio3_001751
KBioGR_002030
KBioSS_001685
NSC26685
PHEOPHYTIN
SPBio_000630
SpecPlus_000601
Spectrum2_000635
Spectrum3_000716
Spectrum4_001705
Spectrum_001205

Target

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Uniprot ID:Q62710_RAT
Synonyms:
Nitric oxide synthase
EC-Numbers:-
Organism:Rat
Rattus norvegicus
PDB IDs:-

Binding Affinities:

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

References:

15368447
Bilirubin inhibits iNOS expression and NO production in response to endotoxin in rats.. Weizheng W Wang; Darcey L H Smith; Stephen D Zucker (2004) Hepatology (Baltimore, Md.) display abstract
The inducible isoform of heme oxygenase (HO), HO-1, has been shown to play an important role in attenuating tissue injury. Because HO-1 catalyzes the rate-limiting step in bilirubin synthesis, we examined the hypothesis that bilirubin is a key mediator of HO-1 cytoprotection, employing a rat model of endotoxemia. Bilirubin treatment resulted in improved survival and attenuated liver injury in response to lipopolysaccharide infusion. Serum levels of NO and tumor necrosis factor alpha, key mediators of endotoxemia, and hepatic inducible nitric oxide synthase (iNOS) expression were significantly lower in bilirubin-treated rodents versus control animals. Both intraperitoneal and local administration of bilirubin also was found to ameliorate hindpaw inflammation induced by the injection of lambda-carrageenan. Consistent with in vivo results, bilirubin significantly inhibited iNOS expression and suppressed NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. In contrast, bilirubin treatment induced a threefold increase in LPS-mediated prostaglandin synthesis in the absence of significant changes in cyclooxygenase expression or activity, suggesting that bilirubin enhances substrate availability for eicosanoid synthesis. Bilirubin had no effect on LPS-mediated activation of nuclear factor kappaB or p38 mitogen-activated protein kinase, consistent with a nuclear factor kappaB-independent mechanism of action. Taken together, these data support a cytoprotective role for bilirubin that is mediated, at least in part, through the inhibition of iNOS expression and, potentially, through stimulation of local prostaglandin E2 production. In conclusion, our findings suggest a role for bilirubin in mollifying tissue injury in response to inflammatory stimuli and support the possibility that the phenomenon of "jaundice of sepsis" represents an adaptive physiological response to endotoxemia. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).