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A Selective MAP3K1 Inhibitor Facilitates Discovery of NPM1 as a Member of the Network
Lidia Boghean1, Sarbjit Singh1, Kiran K Mangalaparthi2
1Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Abstract:
The quinoxaline core is found in several biologically active compounds, with Erdafitinib being the first FDA-approved quinoxaline derivative that targets a kinase and exhibits anti-cancer properties. We previously reported a quinoxaline analog (84) that displayed anti-cancer effects by inhibiting IKKβ, a key kinase in the NFκB pathway. Here, we present the synthesis of a regioisomer (51-106) and its characterization as a selective MAP3K1 inhibitor with improved metabolic stability and oral bioavailability. We used the small molecule MAP3K1 inhibitor in a proteomics study that identified NPM1 as a member of the MAP3K1 network.
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