Structure-based design of a dual-warhead covalent inhibitor of FGFR4

Xiaojuan Chen; Huiliang Li; Qianmeng Lin; Shuyan Dai; Sitong Yue; Lingzhi Qu; Maoyu Li; Ming Guo; Hudie Wei; Jun Li; Longying Jiang; Guangyu Xu; Yongheng Chen

doi:10.1038/s42004-022-00657-9

Communications Chemistry (Mar 2022)

Structure-based design of a dual-warhead covalent inhibitor of FGFR4

Xiaojuan Chen,
Huiliang Li,
Qianmeng Lin,
Shuyan Dai,
Sitong Yue,
Lingzhi Qu,
Maoyu Li,
Ming Guo,
Hudie Wei,
Jun Li,
Longying Jiang,
Guangyu Xu,
Yongheng Chen

Affiliations

Xiaojuan Chen: Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University
Huiliang Li: Key Laboratory of Chemical Biology and Traditional Chinese Medicine, Ministry of Educational of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University
Qianmeng Lin: Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University
Shuyan Dai: Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University
Sitong Yue: Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University
Lingzhi Qu: Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University
Maoyu Li: Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University
Ming Guo: Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University
Hudie Wei: Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University
Jun Li: Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University
Longying Jiang: Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University
Guangyu Xu: Key Laboratory of Chemical Biology and Traditional Chinese Medicine, Ministry of Educational of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University
Yongheng Chen: Department of Oncology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University

DOI: https://doi.org/10.1038/s42004-022-00657-9
Journal volume & issue: Vol. 5, no. 1
pp. 1 – 7

Abstract

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Fibroblast growth factor receptor 4 (FGFR4) is a promising target for the treatment of hepatocellular carcinoma, but current FGFR4 covalent inhibitors target only one of the two cysteine residues (Cys477 or Cys552) that provide FGFR4-specificity. Here, a dual-warhead covalent FGFR4 inhibitor that can covalently target both cysteine residues of FGFR4 is reported, and strong selectivity for FGFR4 is observed.

Published in Communications Chemistry

ISSN: 2399-3669 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science: Chemistry
Website: https://www.nature.com/commschem

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