Target Validation Information
TTD ID	T32335
Target Name	Inhibitor of nuclear factor kappa-B kinase (IKK)
Type of Target	Patented-recorded
Drug Potency against Target	MLN0415	Drug Info	IC50 = 300 nM
Action against Disease Model	MLN0415	Drug Info	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.	[1]
References
REF 1	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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