Small molecule activation of PKM2 in cancer cells induces serine auxotrophy

Kung, Charles, Hixon, Jeff, Choe, Sung, Marks, Kevin, Gross, Stefan, Murphy, Erin, DeLaBarre, Byron, Cianchetta, Giovanni +23 more·2012·Chemistry & Biology

Cited by (194)

Items 101–194 of 194

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  2. Targeting energy metabolism to eliminate cancer cells
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  3. Pyruvate kinase activators as a therapy target: a patent review 2011-2017
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  4. The roles of molecular chaperones in regulating cell metabolism
    Matthew J. Binder, Anthony M. Pedley · 2023 · FEBS Letters
  5. The cysteine residue at 424th of pyruvate kinase M2 is crucial for tetramerization and responsiveness to oxidative stress
    So Masaki, Kozue Hashimoto, Daiki Kihara, Chizuru Tsuzuki, Naoyuki Kataoka, Kenji Suzuki · 2020 · Biochemical and Biophysical Research Communications
  6. Identification of a new pyruvate kinase M2 isoform ( PKM 2) activator for the treatment of non‐small‐cell lung cancer ( NSCLC )
    Runze Li, Xing‐Xing Fan, Danfeng Shi, Guo‐Yuan Zhu, Yuwei Wang, Lianxiang Luo, Hudan Pan, Xiaojun Yao, Elaine Lai‐Han Leung, Liang Liu · 2018 · Chemical Biology & Drug Design
  7. Targeting Nutrient Dependency in Cancer Treatment
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  8. Metabolic switch in cancer – Survival of the fittest
    Hans Raskov, Shruti Gaggar, Asma Tajik, Adile Orhan, Ismail Gögenür · 2022 · European Journal of Cancer
  9. Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators
    Ridong Li, Xianling Ning, Shuo Zhou, Zhiqiang Lin, Xingyu Wu, Hong Chen, Xinyu Bai, Xin Wang, Zemei Ge, Runtao Li et al. · 2017 · European Journal of Medicinal Chemistry
  10. Nuclear Pyruvate Kinase M2 (PKM2) Contributes to Phosphoserine Aminotransferase 1 (PSAT1)-Mediated Cell Migration in EGFR-Activated Lung Cancer Cells
    Rumeysa Biyik‐Sit, Traci L. Kruer, Susan M. Dougherty, James A. Bradley, Daniel Wade Wilkey, Michael L. Merchant, John O. Trent, Brian F. Clem · 2021 · Cancers
  11. Activation of pyruvate kinase as therapeutic option for rare hemolytic anemias: Shedding new light on an old enzyme
    Myrthe J. van Dijk, Jonathan R.A. de Wilde, Marije Bartels, Kevin H.M. Kuo, Andreas Birkedal Glenthøj, Minke A.E. Rab, Eduard Johannes van Beers, Richard van Wijk · 2023 · Blood Reviews
  12. Emerging Approaches for Targeting Metabolic Vulnerabilities in Malignant Glioma
    Peter M. Clark, Wilson X. Mai, Timothy Francis Cloughesy, David A. Nathanson · 2016 · Current Neurology and Neuroscience Reports
  13. Glioblastomas: Hijacking Metabolism to Build a Flexible Shield for Therapy Resistance
    Justine Bailleul, Erina Vlashi · 2023 · Antioxidants and Redox Signaling
  14. Recent Advances on PKM2 Inhibitors and Activators in Cancer Applications
    Peng Chen, Liang Lou, Bigyan Sharma, Mengchu Li, Chengliang Xie, Fen Yang, Yihang Wu, Qicai Xiao, Liqian Gao · 2023 · Current Medicinal Chemistry
  15. Targeting Metabolic Vulnerabilities to Combat Drug Resistance in Cancer Therapy
    Taranatee Khan, M. K. Nagarajan, Irene Kang, Chunjing Wu, Medhi Wangpaichitr · 2025 · Journal of Personalized Medicine
  16. Proteins moonlighting in tumor metabolism and epigenetics
    Lei Lv, Qun‐Ying Lei · 2021 · Frontiers of Medicine
  17. Tuning liver pyruvate kinase activity up or down with a new class of allosteric modulators
    Amalyn Nain‐Perez, Oscar Nilsson, Aleksei Lulla, Liliana Håversen, P. Brear, Sara Liljenberg, Marko Hyvönen, Jan Borén, Morten Grøtli · 2023 · European Journal of Medicinal Chemistry
  18. A new class of HIV-1 inhibitors and the target identification via proteomic profiling
    Ying-Zi Ge, Bin Zhou, Ruoxuan Xiao, Xiaojing Yuan, Hu Zhou, Yechun Xu, Mark A. Wainberg, Ying-Shan Han, Jian‐Min Yue · 2018 · Science China Chemistry
  19. Hidden allosteric sites and De-Novo drug design
    Ashfaq Ur Rehman, Shaoyong Lu, Abdul Aziz Khan, Beenish Khurshid, Salman Rasheed, Abdul Wadood, Jian Zhang · 2021 · Expert Opinion on Drug Discovery
  20. Potential Allosteric Sites Captured in Glycolytic Enzymes Via Residue-Based Network Models: Phosphofructokinase, Glyceraldehyde-3-Phosphate Dehydrogenase and Pyruvate Kinase
    Metehan Çelebi, Tuğçe İnan, Özge Kürkçüoğlu, Ebru Demet Akten · 2021 · Biophysical Chemistry
  21. Computer‐aided identification of a novel pyruvate kinase M2 activator compound
    Yuanyuan Li, Minyue Bao, Chunlan Yang, Jiao Chen, Shu Wen Zhou, Rong Sun, Chuanfang Wu, Xin Li, Jinku Bao · 2018 · Cell Proliferation
  22. A Review on the Role of Pyruvate Kinase M2 in Cancer: From Metabolic Switch to Transcriptional Regulation
    Zulfareen, Aaliya Taiyab, Gulam Mustafa Hasan, Md. Imtaiyaz Hassan · 2025 · International Journal of Biological Macromolecules
  23. Design, Synthesis and Biological Evaluation of Quinoline-8-Sulfonamides as Inhibitors of the Tumor Cell-Specific M2 Isoform of Pyruvate Kinase: Preliminary Study
    Krzysztof Marciniec, Zuzanna Rzepka, Elwira Chrobak, Stanisław Boryczka, Małgorzata T Latocha, Dorota Małgorzata Wrześniok, Artur Beberok · 2023 · Molecules
  24. Synthesis of novel sulfonamide derivatives containing pyridin-3-ylmethyl 4-(benzoyl)piperazine-1-carbodithioate moiety as potent PKM2 activators
    Ridong Li, Xianling Ning, Jianan He, Zhiqiang Lin, Yue Su, Runtao Li, Yuxin Yin · 2021 · Bioorganic Chemistry
  25. Tumor pyruvate kinase M2: A promising molecular target of gastrointestinal cancer
    Guo Chen, Li Guan, Jianing Hou, Xingming Deng, Sheng Ao, Zhuofei Li, Guoqing Lyu · 2018 · Chinese Journal of Cancer Research
  26. Serine and glycine metabolism-related gene expression signature stratifies immune profiles of brain gliomas, and predicts prognosis and responses to immunotherapy
    Siliang Chen, Shuxin Zhang, Wentao Feng, Junhong Li, Yunbo Yuan, Wenhao Li, Zhihao Wang, Yuan Yang, Yanhui Liu · 2022 · Frontiers in Pharmacology
  27. Allosteric regulation of metabolism in cancer: endogenous mechanisms and considerations for drug design
    Jamie A. Macpherson, Dimitrios Anastasiou · 2017 · Current Opinion in Biotechnology
  28. Anti‐Warburg effect via generation of ROS and inhibition of PKM2 /β‐catenin mediates apoptosis of lambertianic acid in prostate cancer cells
    Ji‐Na Pak, Hyo‐Jung Lee, Deok Yong Sim, Ji Eon Park, Chi‐Hoon Ahn, Su‐Yeon Park, Jae‐Ho Khil, Bum‐Sang Shim, Bonglee Kim, Sung‐Hoon Kim · 2023 · Phytotherapy Research
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    Yi‐Ru Bai, Xin Yang, Ke-Tong Chen, Xiao-Dan Cuan, Yao‐Dong Zhang, Li Zhou, Li Yang, Hong‐Min Liu, Shuo Yuan · 2024 · European Journal of Medicinal Chemistry
  30. AllohubPy: Detecting Allosteric Signals Through An Information-theoretic Approach
    Oriol Gracia Carmona, Jens Kleinjung, Dimitrios Anastasiou, Chris Oostenbrink, Franca Fraternali · 2025 · Journal of Molecular Biology
  31. PYK-SubstitutionOME: an integrated database containing allosteric coupling, ligand affinity and mutational, structural, pathological, bioinformatic and computational information about pyruvate kinase isozymes
    Liskin Swint‐Kruse, Larissa L Dougherty, Braelyn M. Page, Tiffany C. Wu, Pierce T. O’Neil, Charulata B. Prasannan, Cody Timmons, Qingling Tang, Daniel J. Parente, Shwetha Sreenivasan et al. · 2023 · Database
  32. Roadmap to Pyruvate Kinase M2 Modulation - A Computational Chronicle
    Amit Shard, Saumya Kapoor, Deep Rohan Chatterjee, Moumita Ghosh Chowdhury, Rudradip Das · 2023 · Current Drug Targets
  33. Knowledge-driven design and optimization of potent symmetric anticancer molecules: A case study on PKM2 activators
    Eshika Jaiswal, Christoph Globisch, Alok K. Jain · 2022 · Computers in Biology and Medicine
  34. Regulation of glycolysis and cancer cell proliferation by PKM2 citrullination
    Sébastien Coassolo, Irwin Davidson · 2021 · Molecular & Cellular Oncology
  35. An evaluation of mitapivat for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency
    Andrew B. Song, Hanny T. Al-Samkari · 2022 · Expert Review of Hematology
  36. Modulation of tumour pyruvate kinase M2 and suppression of cancer cell proliferation using natural and synthetic antioxidants
    Saumya Kapoor, Suraj Kutre, Swarali Joshi, Ashutosh Goswami, Amardeep S. G. Singh, Parusu Kavya Teja, Kishori Jadhav, Pooja Tarde, Rohini B. Jadhav, Rohit Raut et al. · 2024 · Journal of Molecular Structure
  37. Roles of Pyruvate Kinase M2 in Pulmonary Diseases: What Do We Know So Far?
    Diandian Li, Lian Liu, Jiangyue Qin, Cheng Shen, Bo Wang · 2025 · Lung
  38. Domesticating Cancer: An Evolutionary Strategy in the War on Cancer
    G. van Niekerk, T. Nell, A. Engelbrecht · 2017 · Frontiers in Oncology
  39. Glucose Metabolism and Carcinogenesis: The Impact of the Tumor Suppressor p53
    Monde McMillan Ntwasa, Ubanako Njende · 2018 · InTech eBooks
  40. Metabolic Reprogramming and Molecular Rewiring in Cancer: Therapeutic Opportunities
    Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya · 2021 · The Indonesian Biomedical Journal
  41. Integrated screening for small molecules interfering with PKM2: a drug repurposing strategy against glioblastoma
    Susan Costantini, Isabella Romeo, Giulia Fanelli, Maria Serena Roca, Gianmarco Gualtieri, Palmina Bagnara, Andrea Polo, Elena Di Gennaro, Francesco Ortuso, Stefano Alcaro et al. · 2025 · Journal of Translational Medicine
  42. Exploring data‐driven chemical SMILES tokenization approaches to identify key protein–ligand binding moieties
    Asu Büşra Temizer, Gökçe Uludoğan, Rıza Özçelik, Taha Koulani, Elif Özkırımlı, Kutlu Ö. Ülgen, Nilgün Karalı, Arzucan Özgür · 2024 · Molecular Informatics
  43. Phosphine‐Catalyzed 1,6‐Addition and Tandem Addition/Self‐Aldol Condensation Reactions of Para‐Quinone Methides with Thiols
    Yuan Zhong, Guichen Li, Dan Zhang, Yuxuan Xie, Long Hao, Zhengjun Cai, Xin Wang · 2024 · European Journal of Organic Chemistry
  44. Selecting the Right Targets for Fragment‐Based Drug Discovery
    Thomas G. Davies, Harren Jhoti, Puja Pathuri, Glyn Williams · 2016 · Methods and principles in medicinal chemistry
  45. ICBS2012 Catalyzes Robust Response from Global Chemical Biology Community
    Margaret A. Johns · 2012 · ACS Chemical Biology
  46. Mitapivat: New dawn in pyruvate kinase deficiency and beyond
    Ritika Khurana, Sangeeta Sanjay Mudaliar · 2024 · Pediatric Hematology Oncology Journal
  47. Cancer Metabolism: A Nexus of Matter, Energy, and Reactive Oxygen Species
    Paul M. Bingham, Shawn D. Stuart, Zuzana Zachar · 2014 · Cancer drug discovery and develogment/Cancer drug discovery and development
  48. Virtual high-throughput screens identifying hPK-M2 inhibitors: Exploration of model extrapolation
    Jonathan Jun Feng Chen, Lyndsey N. Schmucker, Donald P. Visco · 2018 · Computational Biology and Chemistry
  49. Molecular docking analysis of pyruvate kinase M2 with a potential inhibitor from the ZINC database
    Pankaj V. Sharma · 2021 · Bioinformation
  50. Case studies in rare disease small molecule discovery and development
    Darby R. Schmidt, Christopher Vaun Thompson · 2020 · Bioorganic & Medicinal Chemistry Letters
  51. Metabolism‐Regulating Nanomedicines for Cancer Therapy
    Xiao Wu, Shiyi Geng, Jian Yu Yang · 2025 · Advanced NanoBiomed Research
  52. Discovery of 8-quinolinesulfonamide phenylimidazole-based PKM2 agonists for the prevention and delay of aortic dissection
    Junda Li, Yanyan Yang, Lei Cheng, Xu Xu, Ke Zhong, Tao Wang, Kailin Chen, Chi Zhang, Chen He, Jinyi Xu et al. · 2025 · European Journal of Medicinal Chemistry
  53. Evaluation of Anticancer Activity of Novel Sulfanyl-Substituted Hydrazone Compounds in Hepatocellular Carcinoma: In Vitro, In Silico, and In Ovo Studies
    Hatice Başpınar Küçük, Tülay Yıldız, Yaren ARASAN, Buse Meriç AÇAR, Duygu KURTOĞLU, Aslı Kutlu, Remzi Okan Akar, Sinem KILIÇ, Demet GÜL ERYILMAZ, Engin ULUKAYA · 2026 · ACS Omega
  54. In SilicoInvestigation of Potential Pyruvate Kinase M2 Regulators from Traditional Chinese Medicine against Cancers
    Kuan‐Chung Chen, Kuen‐Bao Chen, Hsin‐Yi Chen, Calvin Yu‐Chian Chen · 2014 · BioMed Research International
  55. [Advances in Research on Cell Metabolic Interactions in the Tumor Microenvironment].
    Pengfei Wu, Zhi Yang, Qingyan Li, Denian Wang · 2024 · PubMed Central
  56. The potential roles of PKM2 in cerebrovascular diseases
    Ling Ma, H.C. Li, Hu Xu, Dianwei Liu · 2024 · International Immunopharmacology
  57. Small-Molecule Reprogramming of Cancer Metabolism
    Matthew R. Pratt · 2012 · Chemistry & Biology
  58. Local effects of Linoorbitides and enterolactone On intestinal epithelial functions
    Ahmed A. Almousa · 2017 · University Library - University of Saskatchewan (University of Saskatchewan)
  59. Mitapivat: a step forward across different hemolytic diseases
    Mohammad Hassan Hodroj, Joseph Klim, Nicole Charbel, Ali T. Taher · 2025 · Expert Opinion on Emerging Drugs
  60. The Role of NPM-ALK Signaling in Tumor Cell Metabolism.
    Scott McDonnell · 2013 · Deep Blue (University of Michigan)
  61. Abstract 1858: Development of a multiplex panel of biomarkers to assess energy metabolism in cancer.
    Meenakshi P. Balakrishnan, Ralph E. Parchment, Melinda G. Hollingshead, Joseph E. Tomaszewski, Robert J. Kinders, James H. Doroshow, Apurva K. Srivastava · 2013 · Cancer Research
  62. Study of regulatory mechanisms of glycolytic and gluconeogenic enzymes
    Meng Yuan · 2016 · Edinburgh Research Archive (University of Edinburgh)
  63. Functional consequence of PSAT1 association on PKM2's inherent enzymatic activity.
    Alexis A. Vega · 2018
  64. Investigating a novel function for phosphoserine aminotransferase 1 (PSAT1) in epidermal growth factor receptor (EGFR)-mediated lung tumorigenesis.
    Rumeysa Biyik‐Sit · 2021
  65. Faculty Opinions recommendation of Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction.
    Fan Fan Hou, Jing Nie · 2017 · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
  66. Data from ASO-Based PKM Splice-Switching Therapy Inhibits Hepatocellular Carcinoma Growth
    Wai Kit Ma, Dillon M. Voss, Juergen Scharner, Ana S.H. Costa, Kuan‐Ting Lin, Hyun Yong Jeon, John Erby Wilkinson, Michaela Jackson, Frank Rigo, C. Frank Bennett et al. · 2023
  67. Arginine-depleting Enzymes, A Potential Treatment Option for Tumors With Arginine Auxotrophy : A Review
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  68. In Silico Screening of Sulfonamide Derivatives against Glycolytic Enzymes Reveals Mutation‐Independent Interactions of Sulfisoxazole and Sulfamethazine
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  69. Mitapivat (AG-348): a groundbreaking treatment paradigm for pyruvate kinase deficiency and beyond
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  70. Allohubpy: Detecting Allosteric Signals Through an Information Theoric Approach
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  71. Mitapivat: A Novel Drug Discovery for the Treatment of Hereditary Hemolytic Anaemias
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  72. Research Progress on the Role of PKM2 in the Cell Cycle of Tumor Cells and Immune Cells
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  73. Additional file 1 of Pharmacological activation of pyruvate kinase M2 reprograms glycolysis leading to TXNIP depletion and AMPK activation in breast cancer cells
    Fadi Almouhanna, Biljana Blagojevic, Suzan Can, Ali Ghanem, Stefan Wölfl · 2021 · Figshare
  74. Additional file 3 of Pharmacological activation of pyruvate kinase M2 reprograms glycolysis leading to TXNIP depletion and AMPK activation in breast cancer cells
    Fadi Almouhanna, Biljana Blagojevic, Suzan Can, Ali Ghanem, Stefan Wölfl · 2021 · Figshare
  75. Additional file 2 of Pharmacological activation of pyruvate kinase M2 reprograms glycolysis leading to TXNIP depletion and AMPK activation in breast cancer cells
    Fadi Almouhanna, Biljana Blagojevic, Suzan Can, Ali Ghanem, Stefan Wölfl · 2021 · Figshare
  76. Additional file 4 of Pharmacological activation of pyruvate kinase M2 reprograms glycolysis leading to TXNIP depletion and AMPK activation in breast cancer cells
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  77. Complexe SWI/SNF et cancer _ Altérations génétiques et anomalies métaboliques
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  88. BindingDB Entry 50016842: A Perspective on Medicinal Chemistry Approaches for Targeting Pyruvate Kinase M2.
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  89. BindingDB Entry 50022202: A comprehensive review of new small molecule drugs approved by the FDA in 2022: Advance and prospect.
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  90. BindingDB Entry 50046285: An update on therapeutic opportunities offered by cancer glycolytic metabolism.
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  91. BindingDB Entry 50003593: Tumor pyruvate kinase M2 modulators: a comprehensive account of activators and inhibitors as anticancer agents.
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  92. BindingDB Entry 50019576: Tuning liver pyruvate kinase activity up or down with a new class of allosteric modulators.
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  93. BindingDB Entry 50019829: PKM2/PDK1 dual-targeted shikonin derivatives restore the sensitivity of EGFR-mutated NSCLC cells to gefitinib by remodeling glucose metabolism.
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  94. Metabolic Adaptation in Reprogrammed Cancer Cells
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