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ID: ALA4431355

Journal: Bioorg Med Chem Lett

Title: Design and synthesis of benzylpiperidine inhibitors targeting the menin-MLL1 interface.

Authors: Ren J, Xu W, Tang L, Su M, Chen D, Chen YL, Zang Y, Li J, Shen J, Zhou Y, Xiong B.

Abstract: Menin is an essential oncogenic cofactor for mixed lineage leukemia (MLL)-mediated leukemogenesis, functioning through its direct interaction with MLL1 protein. Therefore, targeting the menin-MLL1 protein-protein interface represents a promising strategy to block MLL-mediated leukemogenesis. On the basis of co-crystal structure analysis, starting from thienopyrimidine chemotype, we have investigated the detailed structure-activity relationship of the piperazinyl-dihydrothiazole moiety. Several compounds were found with potent inhibitory activity against menin and better activities in cell-based experiments than MI-2-2. Molecular docking analysis revealed a less explored subpocket, which could be used for the design of new menin-MLL1 inhibitors.

CiteXplore: 27528435

DOI: 10.1016/j.bmcl.2016.07.074