Research progress of cellular oxygen sensor FIH inhibitors
10.11665/j.issn.1000-5048.2025051301
- VernacularTitle:细胞氧感受器FIH抑制剂的研究进展
- Author:
Yue WU
1
;
Xiaojin ZHANG
Author Information
1. 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
- Publication Type:Journal Article 期刊文章
- Keywords:
cellular oxygen pathway;
FIH inhibitor;
lipid metabolic disorders;
2OG oxygenases
- From:
Journal of China Pharmaceutical University
2026;57(2):133-143
- CountryChina
- Language:Chinese
-
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.
