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Article

Discovery of N-Trisubstituted Pyrimidine Derivatives as Type I RET and RET Gatekeeper Mutant Inhibitors with a Novel Kinase Binding Pose.

Journal of medicinal chemistry - 27 Jan 2022

Zhang Lingtian, Moccia Marialuisa, Briggs David C, Bharate Jaideep B, Lakkaniga Naga Rajiv, Knowles Phillip, Yan Wei, Tran Phuc, Kharbanda Anupreet, Wang Xiuqi, Leung Yuet-Kin, Frett Brendan, Santoro Massimo, McDonald Neil Q, Carlomagno Francesca, Li Hong-Yu

Abstract excerpt

Mutations of the rearranged during transfection (RET) kinase are frequently reported in cancer, which make it as an attractive therapeutic target. Herein, we discovered a series of N-trisubstituted pyrimidine derivatives as potent inhibitors for both wild-type (wt) RET and RETV804M, which is a resistant mutant for several FDA-approved inhibitors. The X-ray structure of a representative inhibitor with RET revealed...

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Identifiers

PMID: 35081714
DOI: 10.1021/acs.jmedchem.1c01280
PMCID: PMC10536133

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-08.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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Discovery of N-Trisubstituted Pyrimidine Derivatives as Type I RET and RET Gatekeeper Mutant Inhibitors with a Novel Kinase Binding Pose.PMID 35081714Read ↗

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