A Selective MAP3K1 Inhibitor Facilitates Discovery of NPM1 as a Member of the Network

Authors

Lidia Boghean, University of Nebraska Medical Center
Sarbjit Singh, University of Nebraska Medical Center
Kiran K. Mangalaparthi, Mayo Clinic
Smitha Kizhake, University of Nebraska Medical Center

Document Type

Article

Publication Title

Molecules

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.

DOI

10.3390/molecules30092001

Publication Date

5-1-2025

Recommended Citation

Boghean, Lidia; Singh, Sarbjit; Mangalaparthi, Kiran K.; and Kizhake, Smitha, "A Selective MAP3K1 Inhibitor Facilitates Discovery of NPM1 as a Member of the Network" (2025). Open Access archive. 13332.
https://impressions.manipal.edu/open-access-archive/13332