Work

PHGDH as a therapeutic node: Natural modulators from TCM, degradation pathways, and emerging TPD strategies

Year: 2025

Type: article

Abstract: Phosphoglycerate dehydrogenase (PHGDH) has emerged as a promising therapeutic target due to its critical roles in the pathogenesis of cancer and neurological disorders. Targeting PHGDH holds significant theoretical and translational potential for cancer therapy and the amelioration of cognitive impairments. However, currently available PHGDH inhibitors are limited in number and primarily function through inhibition of the enzyme's catalytic activity. This review systematically summarizes PHGDH modulators identified from traditional Chinese medicine, including both inhibitors and activators, and presents a detailed analysis of their structure-activity relationships (SAR) and mechanisms of action. It also comprehensively outlines the signaling pathways that regulate PHGDH degradation through the ubiquitin-proteasome system and autophagy-lysosome pathway. Importantly, it also discusses emerging targeted protein degradation (TPD) technologies, including PROTACs, LYTACs, AUTACs, and ATTECs. The development of these frontier technologies has opened new pathways for mitigating the limitations of existing inhibitors.

Source: Pharmacological Research

DOI: 10.1016/j.phrs.2025.108079

Authors: Song-Song Shi, Yu-Dan Du, Si-Yi Chen, Wen Zhang, Guo-Wu Rao, Quan Zheng

Institutions: Zhejiang University of Technology, Wenzhou Medical University, Quzhou City People's Hospital

Language: English

Topic: Cancer, Hypoxia, and Metabolism

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,130