| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T32335 | ||||
| Target Name | Inhibitor of nuclear factor kappa-B kinase | ||||
| Target Type | Research |
||||
| Drug Potency against Target | MLN0415 | Drug Info | IC50 = 300 nM | ||
| Action against Disease Model | MLN0415 | Inhibition of constitutive IKK activity by BMS-345541 resulted in the reduction of NF-kappaB activity, CXCL1 chemokine secretion by cultured melanoma cells and melanoma cell survival in vitro and in vivo. The effect of BMS-345541 on t uMor cell growth was through mitochondria-mediated apoptosis, based on the release of apoptosis-inducing factor, dissipation of mitochondrial membrane potential, and reduced ratio of B cell lymphoma gene-2 (Bcl-2)/Bcl-associated X protein (Bax) in mitochondria. The BMS-345541 execution of apoptosis was apoptosis-inducing factor-dependent, but largely caspase-independent. | [552580] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | LPS/survival significant decrease; Liver degeneration;Airway epitheli uM: diminished inflammatory response;Myeloid cells: resistance to Streptococcus pne uMoniae significant increase;increased macrophage activation in response to LPS in vivo; Intestinal inflammation in IL-10-deficient mices; In vivo phenotype:Increased insulin sensitivity in heterozygous null mice | ||||
| References | |||||
| Ref 552580 | BMS-345541 targets inhibitor of kappaB kinase and induces apoptosis in melanoma: involvement of nuclear factor kappaB and mitochondria pathways. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):950-60. | ||||
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