ArticleProceedings of the National Academy of Sciences of the United States of America2019
An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 60 citations in OpenAlex.
- Targeting PGAM1 Y119 phosphorylation resensitizes non-small-cell lung cancer to cisplatin therapy by promoting oxidative stress and DNA damage.The Journal of biological chemistry · 2026Article
- PGAM1 rheostat in glycolysis and autophagy.Nature cell biology · 2026Article
- Mitophagy-Competent Cancer-Associated Fibroblasts Fuel Chemoresistance by Rewiring Pyrimidine Metabolism in Pancreatic Cancer.Cancer research · 2026Article
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- REEP6 promotes colorectal cancer glycolysis and tumorigenesis through PRMT5-mediated PGAM1 arginine methylation.Acta pharmaceutica Sinica. B · 2026Article
- PLA-THF-PEG nanoparticles Co-encapsulating AV3 and KH3 for synergistic pancreatic cancer therapy via stromal remodeling and metabolic inhibition.Frontiers in pharmacology · 2026Article
- The function of phosphoglycerate mutase 1 (PGAM1) and its role in diseases.Frontiers in molecular biosciences · 2026Review
- TOPBP1 as a potential predictive biomarker for enhanced combinatorial efficacy of olaparib and AZD6738 in PDAC.Cell & bioscience · 2025Article
- CircRNA PGAM1 Promotes the Migration and Invasion of Pancreatic Adenocarcinoma Cells by Activating the AKT/mTOR Signaling Pathway.Molecular biotechnology · 2024Article
- Emerging mechanisms and promising approaches in pancreatic cancer metabolism.Cell death & disease · 2024Review
- Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages.Cancer gene therapy · 2024Article
- PKM2 functions as a histidine kinase to phosphorylate PGAM1 and increase glycolysis shunts in cancer.The EMBO journal · 2024Article
- Energy stress-induced circDDX21 promotes glycolysis and facilitates hepatocellular carcinogenesis.Cell death & disease · 2024Article
- The Wnt-pathway corepressor TLE3 interacts with the histone methyltransferase KMT1A to inhibit differentiation in Rhabdomyosarcoma.Oncogene · 2024Article
- LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance.International journal of biological sciences · 2024Review
- Pan-Cancer Analysis of PGAM1 and Its Experimental Validation in Uveal Melanoma Progression.Journal of Cancer · 2024Article
- Oncogenic KRAS triggers metabolic reprogramming in pancreatic ductal adenocarcinoma.Journal of translational internal medicine · 2023Article
- PGAM1 Inhibition Promotes HCC Ferroptosis and Synergizes with Anti-PD-1 Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- MicroRNA-324-3p inhibits osteosarcoma progression by suppressing PGAM1-mediated aerobic glycolysis.Cancer science · 2023Article
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Authors and funding
32 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structure-guided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided "proof of concept" for the potential application of metabolic treatment in clinical practice.
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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.