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Pharmacol. Rev., Available online 5 February 2025, 100045 | https://doi.org/10.1016/j.pharmr.2025.100045
Heme-thiolate monooxygenase cytochrome P450 1B1, an old dog with many new tricks
Jong-Won Kim 1,4∗, Hung-Chun Tung 1,4∗, Bin Yang 1, Rajat Pant 1, Xiuchen Guan 2, Ye Feng 3, Wen Xie 1,4∗
1Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA
2Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, 100069, China
3Department of Endocrinology and Metabolic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003 China
4Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA
∗These authors contributed equally to the writing of this article.
Corresponding Author: Wen Xie, MD, Ph.D
1Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA
2Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing, 100069, China
3Department of Endocrinology and Metabolic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003 China
4Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA
∗These authors contributed equally to the writing of this article.
Corresponding Author: Wen Xie, MD, Ph.D
Abstract
Cytochrome P450 (CYP) 1B1 is a heme-thiolate monooxygenase traditionally recognized for its xenobiotic functions and extrahepatic expressions. Recent studies have suggested that CYP1B1 is also expressed in hepatic stellate cells, immune cells, endothelial cells, and fibroblasts within the tumor microenvironment, as well as tumor cells themselves. CYP1B1 is responsible for the metabolism of a wide range of substrates, including xenobiotics such as drugs, environmental chemicals, and endobiotics such as steroids, retinol, and fatty acids. Consequently, CYP1B1 and its associated exogenous and endogenous metabolites have been critically implicated in the pathogenesis of many diseases. Understanding the mode of action of CYP1B1 in different pathophysiological conditions and developing pharmacological inhibitors that allow for systemic or cell-type-specific modulation of CYP1B1 may pave the way for novel therapeutic opportunities. This review highlights the significant role of CYP1B1 in maintaining physiological homeostasis and provides a comprehensive discussion of recent advancements in our understanding of CYP1B1's involvement in the pathogenesis of diseases such as fibrosis, cancer, glaucoma, and metabolic disorders. Finally, the review emphasizes the therapeutic potential of targeting CYP1B1 for drug development, particularly in the treatment and prevention of cancers and liver fibrosis.
논문정보
- Review Paper
- 2025년 02월 (BRIC 등록일 2025-02-12)
- 국외 연구진
- 의약학 > 약리의학
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