Target Validation Information
Target ID T83145
Target Name Nuclear factor NF-kappa-B
Target Type
Successful
Drug Potency against Target ATRIPLICIOLIDTIGLATE Drug Info IC100 = 5000 nM [1]
ARTORIGIDIN A Drug Info IC50 = 2000 nM [2]
ROCAGLAMIDE Drug Info IC50 = 4000 nM [2]
ARTOBILOXANTHONE Drug Info IC50 = 3700 nM [2]
4-nitro-N-(quinolin-8-yl)benzenesulfonamide Drug Info IC50 = 1500 nM [3]
15-DEOXYBUDLEIN A Drug Info IC100 = 5000 nM [1]
1beta-methoxy-miller-9Z-enolide Drug Info IC100 = 10000 nM [4]
Miller-9E-enolide Drug Info IC100 = 5000 nM [4]
ISOGOIAZENSOLIDE Drug Info IC100 = 10000 nM [1]
MOLEPHANTIN Drug Info IC100 = 10000 nM [1]
MOLEPHANTININ Drug Info IC100 = 10000 nM [1]
2-oxoguaia-1,4,11(13)-trien-12,8alpha-olide Drug Info IC100 = 10000 nM [4]
BUDLEIN A Drug Info IC100 = 5000 nM [1]
15-ACETOXY-EREMANTHOLIDE B Drug Info IC100 = 5000 nM [1]
SCANDENOLIDE Drug Info IC100 = 10000 nM [1]
Sulfasalizine Drug Info IC50 = 89 nM [5]
HELENALIN Drug Info IC100 = 10000 nM [1]
15-deoxygoiazensolide Drug Info IC100 = 10000 nM [4]
ATRIPLICIOLIDTIGLATE Drug Info IC100 = 5000 nM [4]
Helenalin-2-methylbutyrate Drug Info IC100 = 10000 nM [4]
9-methyl-5H-6-thia-4,5-diaza-chrysene 6,6-dioxide Drug Info IC50 = 600 nM [3]
7-hydroxycostunolide Drug Info IC100 = 10000 nM [4]
ENHYDRIN Drug Info IC100 = 10000 nM [4]
15-isobutyrylmiguanin Drug Info IC100 = 12500 nM [4]
SCANDENOLIDE Drug Info IC100 = 10000 nM [4]
4beta,15-epoxy-miller-9Z-enolide Drug Info IC100 = 5000 nM [4]
Miller-9Z-enolide Drug Info IC100 = 10000 nM [4]
4beta,15-epoxy-miller-9E-enolide Drug Info IC100 = 5000 nM [4]
HELENALINMETHACRYLATE Drug Info IC100 = 5000 nM [4]
4,5-ISOBUDLEIN A Drug Info IC100 = 10000 nM [4]
2beta-methoxy-2-deethoxyphantomolin Drug Info IC100 = 10000 nM [4]
9alpha-acetoxy-miller-1(10)Z-enolide Drug Info IC100 = 10000 nM [4]
15-ACETOXY-EREMANTHOLIDE B Drug Info IC100 = 5000 nM [4]
MOLEPHANTININ Drug Info IC100 = 10000 nM [4]
ISOGOIAZENSOLIDE Drug Info IC100 = 10000 nM [4]
15-DEOXYBUDLEIN A Drug Info IC100 = 5000 nM [4]
3,4-epoxydehydroleucodin Drug Info IC100 = 5000 nM [4]
HELENALIN Drug Info IC100 = 10000 nM [4]
MOLEPHANTIN Drug Info IC100 = 10000 nM [4]
2-oxoguaia-1,4(15), 11(13)-trien-12,8beta-olide Drug Info IC100 = 5000 nM [4]
CENTRATHERIN Drug Info IC100 = 5000 nM [4]
9-fluoro-5H-6-thia-4,5-diaza-chrysene 6,6-dioxide Drug Info IC50 = 1700 nM [3]
N-(quinolin-8-yl)thiophene-2-sulfonamide Drug Info IC50 = 3600 nM [3]
2-amino-N-(quinolin-8-yl)benzenesulfonamide Drug Info IC50 = 2000 nM [3]
BUDLEIN A Drug Info IC100 = 5000 nM [4]
5-chloro-N-(quinolin-8-yl)thiophene-2-sulfonamide Drug Info IC50 = 1300 nM [3]
5-bromo-N-(quinolin-8-yl)thiophene-2-sulfonamide Drug Info IC50 = 1100 nM [3]
2-nitro-N-(quinolin-8-yl)benzenesulfonamide Drug Info IC50 = 3200 nM [3]
5H-6-thia-4,5-diaza-chrysene 6,6-dioxide Drug Info IC50 = 1000 nM [3]
9-chloro-5H-6-thia-4,5-diaza-chrysene 6,6-dioxide Drug Info IC50 = 1100 nM [3]
Action against Disease Model Omtriptolide Triptolide significantly impairs DC-mediated chemoattraction of neutrophils and T cells both in vitro and in vivo by suppressing DC production of CC and CXC chemokines includingMIP-1alpha, MIP-1beta, MCP-1, RANTES, TARC, and IP-10 in response to LPS. triptolide-mediated inhibition of NF-kappaB activation, Stat3 phosphorylation and increase of SOCS1 expression in DC may be involved in the inhibitory effect of triptolide [6] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations To clarify the role of NF-kappaB p50 in postinfarct left ventricular remodeling, myocardial infarction was induced in wild-type 129Bl6 mice and NF-kappaB p50-deficient mice. Without affecting infarct size, deletion of NF-kappaB p50 markedly increased the extent of expansive remodeling (end-diastolic vol uMe: 176+/-13 microL versus 107+/-11 microL; P=0.003) and aggravated systolic dysfunction (left ventricular ejection fraction: 16.1+/-1.5% versus 24.7+/-3.7%; P=0.029) in a 28-day time period. Interstitial fibrosis and hypertrophy in the noninfarcted myocardi uM was increased in NF-kappaB p50 knockout mice. In the infarct area, a lower collagen density was observed, which was accompanied by an increased n uMber of macrophages, higher gelatinase activity and increased inflammatory cytokine expression. In conclusion, targeted deletion of NF-kappaB p50 results in enhanced cardiac remodeling and functional deterioration following myocardial infarction by increasing matrix remodeling and inflammation. [6]
References
REF 1J Med Chem. 2004 Nov 18;47(24):6042-54.Quantitative structure-activity relationship of sesquiterpene lactones as inhibitors of the transcription factor NF-kappaB.
REF 2J Nat Prod. 2010 May 28;73(5):949-55.Cytotoxic and NF-kappaB inhibitory constituents of Artocarpus rigida.
REF 3Bioorg Med Chem Lett. 2008 Jan 1;18(1):329-35. Epub 2007 Oct 30.Identification of N-(quinolin-8-yl)benzenesulfonamides as agents capable of down-regulating NFkappaB activity within two separate high-throughput screens of NFkappaB activation.
REF 4J Med Chem. 2006 Apr 6;49(7):2241-52.Development of a structural model for NF-kappaB inhibition of sesquiterpene lactones using self-organizing neural networks.
REF 5Novel sulfasalazine analogues with enhanced NF-kB inhibitory and apoptosis promoting activity. Apoptosis. 2005 May;10(3):481-91.
REF 6Immunosuppressant triptolide inhibits dendritic cell-mediated chemoattraction of neutrophils and T cells through inhibiting Stat3 phosphorylation and NF-kappaB activation. Biochem Biophys Res Commun. 2006 Jul 7;345(3):1122-30. Epub 2006 May 12.

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