Page 7 - 《中国药科大学学报》2026年第2期

学报
Journal of China Pharmaceutical University 2026, 57(2): 133 − 143 133

·综 述·

细胞氧感受器 FIH 抑制剂的研究进展

伍 悦，张晓进 *

（中国药科大学理学院化学系, 江苏省创新药物设计和成药性优化重点实验室, 南京 211198）

摘 要 细胞氧感受器天冬酰胺酰羟化酶（factor inhibiting HIF，FIH）是一种 JmjC 结构域的 2-氧戊二酸和 Fe(II) 依赖性氧
化酶，能够催化缺氧诱导因子 HIF-α 的 C 端转录激活域中特定天冬酰胺残基的羟基化。这一修饰通过降低 HIF 与转录共激
活因子 p300/CBP 的相互作用来抑制其转录活性。FIH 抑制剂因其潜在的代谢调节能力而备受关注，尤其是在改善脂质代谢
性疾病的治疗中表现出显著的治疗潜力。本文详细论述了 FIH 的作用机制及 FIH 在 HIF 活性调控中的生物学功能。此外，
本文还重点综述了 FIH 抑制剂研究进展并进一步探讨了其在脂质代谢性疾病治疗中的应用潜力，为脂质代谢性疾病药物研
发提供新思路。
关键词 细胞氧感知通路；FIH 抑制剂；脂质代谢性疾病；2OG 加氧酶
中图分类号 R914 文献标志码 A 文章编号 1000−5048(2026)02−0133−11
doi：10.11665/j.issn.1000−5048.2025051301

引用本文 伍悦，张晓进. 细胞氧感受器 FIH 抑制剂的研究进展 [J]. 中国药科大学学报，2026，57（2）：133-143.

Cite this article as: WU Yue, ZHANG Xiaojin. Research progress of cellular oxygen sensor FIH inhibitors[J]. J China Pharm Univ, 2026,
57(2): 133-143.

Research progress of cellular oxygen sensor FIH inhibitors

WU Yue, ZHANG Xiaojin *
Department of Chemistry, School of Science, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical
University, Nanjing 211198, China

Abstract The cellular oxygen sensor factor inhibiting HIF (FIH) is a JmjC domain-containing 2-oxoglutarate
and Fe(II)-dependent oxygenase that catalyzes the hydroxylation of specific asparagine residues in the C-terminal
transcriptional activation domain of hypoxia-inducible factor (HIF)-α. This modification inhibits HIF
transcriptional activity by suppressing its interaction with the transcriptional coactivator p300/CBP. FIH
inhibitors have attracted considerable attention due to their potential metabolic regulatory capabilities, particularly
their significant therapeutic potential in improving lipid metabolic disorders. This review provides a detailed
discussion of the catalytic mechanism of FIH and its biological functions in regulating the HIF pathway. In
addition, it highlights recent advances in the development of FIH inhibitors and further explores their potential
applications in the treatment of lipid metabolic diseases, offering new insights for the development of drugs
targeting lipid metabolism disorders.
Key words cellular oxygen pathway; FIH inhibitor; lipid metabolic disorders; 2OG oxygenases

This work was supported by the Young Scientists Fund of National Natural Science Foundation of China (No.82504579); Basic
Research Program of Jiangsu Province (BK20251577); China Postdoctoral Science Foundation (BX20250210); the Excellent Young
Scientists Fund of National Natural Science Foundation of China (No. 82322062)

收稿日期 2025-05-13 * 通信作者 E-mail：zxj@cpu.edu.cn
基金项目 国家自然科学青年基金项目（No.82504579）;江苏省基础研究计划（BK20251577）;中国博士后创新人才支持项目
（BX20250210）;国家自然科学基金优秀青年基金项目（No.82322062）