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

Song-Song Shi1, Du Yu-Dan1, Si-Yi Chen1

  • 1College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, PR China.

Pharmacological Research
|December 25, 2025
PubMed

Insights

This review explores phosphoglycerate dehydrogenase (PHGDH) modulators from traditional Chinese medicine. It highlights novel therapeutic strategies, including targeted protein degradation, for cancer and neurological disorders.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • Phosphoglycerate dehydrogenase (PHGDH) is implicated in cancer and neurological disease pathogenesis.
  • Current PHGDH inhibitors primarily target catalytic activity, with limited options available.
  • PHGDH modulation offers therapeutic potential for cancer and cognitive impairment.

Purpose of the Study:

  • To systematically review PHGDH modulators from traditional Chinese medicine.
  • To analyze structure-activity relationships (SAR) and mechanisms of action of these modulators.
  • To discuss emerging targeted protein degradation (TPD) technologies for PHGDH.

Main Methods:

  • Systematic literature review of traditional Chinese medicine compounds.
  • Analysis of structure-activity relationships (SAR) and mechanisms of action.
  • Review of signaling pathways regulating PHGDH degradation (ubiquitin-proteasome, autophagy-lysosome).

Main Results:

  • Identified various PHGDH inhibitors and activators from traditional Chinese medicine.
  • Detailed SAR and mechanistic insights for identified compounds.
  • Overview of PHGDH degradation pathways and their regulation.

Conclusions:

  • Traditional Chinese medicine offers diverse PHGDH modulators.
  • Emerging TPD technologies like PROTACs present new therapeutic avenues.
  • PHGDH-targeted therapies show promise for cancer and neurological disorders.
Keywords:
Autophagy–Lysosome pathwayNatural productsPhosphoglycerate dehydrogenaseTargeted protein degradation (TPD)Ubiquitin–proteasome system

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