细胞氧感受器FIH抑制剂的研究进展OA
Research progress of cellular oxygen sensor FIH inhibitors
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.
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.
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
医药卫生
细胞氧感知通路FIH抑制剂脂质代谢性疾病2OG加氧酶
cellular oxygen pathwayFIH inhibitorlipid metabolic disorders2OG oxygenases
《中国药科大学学报》 2026 (2)
133-143,11
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)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)
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