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Hepatotoxicity of FDA-approved small molecule kinase inhibitors

Jiang, Haochen, Jin, Ying, Yan, Hao, Xu, Zhifei, Yang, Bo, He, Qiaojun, Luo, Peihua·2021·Expert Opinion on Drug Safety

DOI 10.1080/14740338.2021.1867104

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Abstract

Introduction : Given their importance in cellular processes and association with numerous diseases, protein kinases have emerged as promising targets for drugs. The FDA has approved greater than fifty small molecule kinase inhibitors (SMKIs) since 2001. Nevertheless, severe hepatotoxicity and related fatal cases have grown as a potential challenge in the advancement of these drugs, and the identification and diagnosis of drug-induced liver injury (DILI) are thorny problems for clinicians. Areas covered : This article summarizes the progression and analyzes the significant features in the study of SMKI hepatotoxicity, including clinical observations and investigations of the underlying mechanisms. Expert opinion : The understanding of SMKI-associated hepatotoxicity relies on the development of preclinical models and improvement of clinical assessment. With a full understanding of the role of inflammation in DILI and the mediating role of cytokines in inflammation, cytokines are promising candidates as sensitive and specific biomarkers for DILI. The emergence of three-dimensional spheroid models demonstrates potential use in providing clinically relevant data and predicting hepatotoxicity of SMKIs.

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Authors: Jiang, H., Jin, Y., Yan, H., Xu, Z., Yang, B., He, Q., & Luo, P.
Affiliations: Center for Drug Safety Evaluation and Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou China
Venue: Expert Opinion on Drug Safety
Publisher: Informa UK Limited
Published: 2020-12-27
Volume: 20
Issue: 3
Pages: 335-348
ISSN: 1474-0338
1744-764X
DOI: 10.1080/14740338.2021.1867104
Cited by: 13
References: 95
Language: en
Funders: National Natural Science Foundation of China

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Hepatotoxicity of FDA-approved small molecule kinase inhibitors

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