ArticleActa pharmaceutica Sinica. B2022
Identification of a novel PHGDH covalent inhibitor by chemical proteomics and phenotypic profiling.
Article in Acta pharmaceutica Sinica. B, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 52 citations in OpenAlex.
- PHGDH in cancer: a narrative review of its functions beyond serine metabolism.Translational cancer research · 2026Review
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- Recent advances in proteomic strategies for target identification of traditional Chinese medicine.Journal of pharmaceutical analysis · 2026Review
- Syringin disrupts the DLAT/MYC axis to dampen TAM polarization and suppress hepatocellular carcinoma progression.Acta pharmaceutica Sinica. B · 2026Article
- Review
- PARP1-BCAT2 axis upregulates ABCG1 via histone lactylation to drive acquired PARP inhibitor resistance in prostate cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- L-serine at the crossroads of microbiota, intestinal health, and disorders.Communications biology · 2026Review
- Integrative analysis and functional validation identified palmitoylated PHGDH as a therapeutic target for colon adenocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Resveratrol Induces Proteasomal Degradation of PTPN1 to Enhance Cisplatin Sensitivity in Epstein-Barr Virus-Associated Malignancies.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Amino Acid Metabolic Enzymes in Gastric Cancer: Roles and Mechanisms in Tumorigenesis and Progression.Oncology research · 2026Review
- One-carbon metabolism in cancer: moonlighting functions of metabolic enzymes and anti-tumor therapy.Cancer metastasis reviews · 2025Review
- Corynoline enhances sorafenib sensitivity in hepatocellular carcinoma via NOS3-mediated ROS production.Chinese medicine · 2025Article
- Target discovery-directed pharmacological mechanism elucidation of bioactive natural products.Medical review (2021) · 2025Review
- Target identification of natural products in cancer with chemical proteomics and artificial intelligence approaches.Cancer biology & medicine · 2025Review
- In silico discovery of a novel potential allosteric PI3Kα inhibitor incorporating 2-oxopropyl urea targeting head and neck squamous cell carcinoma.BMC chemistry · 2025Article
- Recent progress in serine metabolism reprogramming in tumors and strategies for serine deprivation.Frontiers in oncology · 2025Review
- Understanding the molecular mechanism responsible for developing therapeutic radiation-induced radioresistance of rectal cancer and improving the clinical outcomes of radiotherapy - A review.Cancer biology & therapy · 2024Review
- E-Cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer.Cancer research · 2024Article
- Review
- Cycling back to folate metabolism in cancer.Nature cancer · 2024Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.