Prakash Radhakrishnan, Vashti C Bryant, Elizabeth C Blowers, Rajkumar N Rajule, Nagsen Gautam, Muhammad M Anwar, Ashley M Mohr, Paul M Grandgenett, Stephanie K Bunt, Jamie L Arnst, Subodh M Lele, Yazen Alnouti, Michael A Hollingsworth, Amarnath Natarajan
PURPOSE: The presence of TNF-α in approximately 50% of surgically resected tumors suggests that the canonical NF-κB and the mTOR pathways are activated. Inhibitor of IκB kinase β (IKKβ) acts as the signaling node that regulates transcription via the p-IκBα/NF-κB axis and regulates translation via the mTOR/p-S6K/p-eIF4EBP axis. A kinome screen identified a quinoxaline urea analog 13-197 as an IKKβ inhibitor. We hypothesized that targeting the NF-κB and mTOR pathways with 13-197 will be effective in malignancies driven by these pathways...
April 15, 2013: Clinical Cancer Research