Tilting the Scales toward EGFR Mutant Selectivity: Expanding the Scope of Bivalent "Type V" Kinase Inhibitors.

doi:10.1021/acs.jmedchem.4c02311

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Article

Tilting the Scales toward EGFR Mutant Selectivity: Expanding the Scope of Bivalent "Type V" Kinase Inhibitors.

Journal of medicinal chemistry - 12 Dec 2024

Wittlinger Florian, Chitnis Surbhi P, Pham Calvin D, Damghani Tahereh, Patel Kishan B, Möllers Mareike, Schaeffner Ilse K, Abidakun Omobolanle A, Deng Matthew Q, Ogboo Blessing C, Rasch Alexander, Beyett Tyler S, Buckley Brian, Feru Frederic, Shaurova Tatiana, Knappe Cornelius, Eck Michael J, Hershberger Pamela A, Scott David A, Brandt Asher L, Laufer Stefan A, Heppner David E

Abstract excerpt

Binding multiple sites within proteins with bivalent compounds is a strategy for developing uniquely active agents. A new class of dual-site inhibitors has emerged targeting the epidermal growth factor receptor (EGFR) anchored to both the orthosteric (ATP) and allosteric sites. Despite proof-of-concept successes, enabling selectivity against oncogenic activating mutations has not been achieved and classifying...

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PMID: 39626019
DOI: 10.1021/acs.jmedchem.4c02311
PMCID: PMC12054702

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