Structural basis for producing selective MAP2K7 inhibitors

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Abstract

Mitogen-activated protein kinase kinase 7 (MAP2K7) in the c-Jun N-terminal kinase signal cascade is an attractive drug target for a variety of diseases. The selectivity of MAP2K7 inhibitors against off-target kinases is a major barrier in drug development. We report a crystal structure of MAP2K7 complexed with a potent covalent inhibitor bearing an acrylamide moiety as an electrophile, which discloses a structural basis for producing selective and potent MAP2K7 inhibitors.

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Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

Preliminary X-ray experiments and diffraction data collection were carried out at the beam line BL17A of the Photon Factory (Proposal No. 2018G040) and at the Osaka University beam line BL44XU of SPring-8 (Proposal No. 2019B6513).

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