Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase PFKFB3

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1. Carlo De Dominicis, Paola Perrotta, Sergio Dall’Angelo, Leonie Wyffels, Steven Staelens, G. R. Y. De Meyer, Matteo Zanda. [18F]ZCDD083: A PFKFB3-Targeted PET Tracer for Atherosclerotic Plaque Imaging. ACS Medicinal Chemistry Letters 2020, 11 (5) , 933-939. https://doi.org/10.1021/acsmedchemlett.9b00677
2. Sarath Babu Nukala, Giovanna Baron, Giancarlo Aldini, Marina Carini, Alfonsina D’Amato. Mass Spectrometry-based Label-free Quantitative Proteomics To Study the Effect of 3PO Drug at Cellular Level. ACS Medicinal Chemistry Letters 2019, 10 (4) , 577-583. https://doi.org/10.1021/acsmedchemlett.8b00593
3. Annaram Thirupathi, Manojkumar Janni, Saravanan Peruncheralathan. Copper Catalyzed Intramolecular N-Arylation of Ketene Aminals at Room Temperature: Synthesis of 2-Amino-3-cyanoindoles. The Journal of Organic Chemistry 2018, 83 (15) , 8668-8678. https://doi.org/10.1021/acs.joc.8b00816
4. Monika Komza, Jesminara Khatun, Jesse D. Gelles, Andrew P. Trotta, Ioana Abraham-Enachescu, Juan Henao, Ahmed Elsaadi, Andriana G. Kotini, Cara Clementelli, JoAnn Arandela, Sebastian El Ghaity-Beckley, Agneesh Barua, Yiyang Chen, Mirela Berisa, Bridget K. Marcellino, Eirini P. Papapetrou, Masha V. Poyurovsky, Jerry Edward Chipuk. Metabolic adaptations to acute glucose uptake inhibition converge upon mitochondrial respiration for leukemia cell survival. Cell Communication and Signaling 2025, 23 (1) https://doi.org/10.1186/s12964-025-02044-y
5. Peiyu Liu, Dandan Sun, Shuchang Zhang, Shimei Chen, Xiaoqian Wang, Huiming Li, Fang Wei. PFKFB3 in neovascular eye disease: unraveling mechanisms and exploring therapeutic strategies. Cell & Bioscience 2024, 14 (1) https://doi.org/10.1186/s13578-024-01205-9
6. Kavit Raval, Neema Jamshidi, Berfin Seyran, Lukasz Salwinski, Raju Pillai, Lixin Yang, Feiyang Ma, Matteo Pellegrini, Juliana Shin, Xia Yang, Slavica Tudzarova. Dysfunctional β-cell longevity in diabetes relies on energy conservation and positive epistasis. Life Science Alliance 2024, 7 (12) , e202402743. https://doi.org/10.26508/lsa.202402743
7. Monika Komza, Jesminara Khatun, Jesse D. Gelles, Andrew P. Trotta, Ioana Abraham-Enachescu, Juan Henao, Ahmed Elsaadi, Andriana G. Kotini, Cara Clementelli, JoAnn Arandela, Sebastian El Ghaity-Beckley, Agneesh Barua, Yiyang Chen, Bridget K. Marcellino, Eirini P. Papapetrou, Masha V. Poyurovsky, Jerry Edward Chipuk. Metabolic Adaptations To Acute Glucose Uptake Inhibition Converge Upon Mitochondrial Respiration For Leukemia Cell Survival. 2024https://doi.org/10.1101/2024.11.20.624567
8. Chunmei CHEN, Xueni WANG, Wenxuan FANG, Jiaqi LIANG, Jian CAI, Dehua YANG, Xiaowei LUO, Chenghai GAO, Xiangxi YI, Yonghong LIU, Xuefeng ZHOU. Talaketides A−G, linear polyketides with prostate cancer cytotoxic activity from the mangrove sediment-derived fungus Talaromyces sp. SCSIO 41027. Chinese Journal of Natural Medicines 2024, 22 (11) , 1047-1056. https://doi.org/10.1016/S1875-5364(24)60659-X
9. Ling Zhou, Juan Li, Juanjuan Wang, Xuping Niu, Junqin Li, Kaiming Zhang. Pathogenic role of PFKFB3 in endothelial inflammatory diseases. Frontiers in Molecular Biosciences 2024, 11 https://doi.org/10.3389/fmolb.2024.1454456
10. Zeinab Kooshan, Lilibeth Cárdenas-Piedra, Judith Clements, Jyotsna Batra. Glycolysis, the sweet appetite of the tumor microenvironment. Cancer Letters 2024, 600 , 217156. https://doi.org/10.1016/j.canlet.2024.217156
11. Tan Zhang, Shengchuan Chen, Liang Li, Yuepeng Jin, Siying Liu, Zhu Liu, Fengyu Shi, Lifen Xie, Panpan Guo, Andrew C. Cannon, Akmal Ergashev, Haiping Yao, Chaohao Huang, Baofu Zhang, Lijun Wu, Hongwei Sun, Siming Chen, Yunfeng Shan, Zhengping Yu, Ezequiel J. Tolosa, Jianghuai Liu, Martin E. Fernandez-Zapico, Feng Ma, Gang Chen. PFKFB3 controls acinar IP3R-mediated Ca2+ overload to regulate acute pancreatitis severity. JCI Insight 2024, 9 (13) https://doi.org/10.1172/jci.insight.169481
12. Daniel Jimenez-Blasco, Jesús Agulla, Rebeca Lapresa, Marina Garcia-Macia, Veronica Bobo-Jimenez, Dario Garcia-Rodriguez, Israel Manjarres-Raza, Emilio Fernandez, Yannick Jeanson, Spiro Khoury, Jean-Charles Portais, Daniel Padro, Pedro Ramos-Cabrer, Peter Carmeliet, Angeles Almeida, Juan P. Bolaños. Weak neuronal glycolysis sustains cognition and organismal fitness. Nature Metabolism 2024, 6 (7) , 1253-1267. https://doi.org/10.1038/s42255-024-01049-0
13. Shintaro Watanuki, Hiroshi Kobayashi, Yuki Sugiura, Masamichi Yamamoto, Daiki Karigane, Kohei Shiroshita, Yuriko Sorimachi, Shinya Fujita, Takayuki Morikawa, Shuhei Koide, Motohiko Oshima, Akira Nishiyama, Koichi Murakami, Miho Haraguchi, Shinpei Tamaki, Takehiro Yamamoto, Tomohiro Yabushita, Yosuke Tanaka, Go Nagamatsu, Hiroaki Honda, Shinichiro Okamoto, Nobuhito Goda, Tomohiko Tamura, Ayako Nakamura-Ishizu, Makoto Suematsu, Atsushi Iwama, Toshio Suda, Keiyo Takubo. Context-dependent modification of PFKFB3 in hematopoietic stem cells promotes anaerobic glycolysis and ensures stress hematopoiesis. eLife 2024, 12 https://doi.org/10.7554/eLife.87674
14. Shintaro Watanuki, Hiroshi Kobayashi, Yuki Sugiura, Masamichi Yamamoto, Daiki Karigane, Kohei Shiroshita, Yuriko Sorimachi, Shinya Fujita, Takayuki Morikawa, Shuhei Koide, Motohiko Oshima, Akira Nishiyama, Koichi Murakami, Miho Haraguchi, Shinpei Tamaki, Takehiro Yamamoto, Tomohiro Yabushita, Yosuke Tanaka, Go Nagamatsu, Hiroaki Honda, Shinichiro Okamoto, Nobuhito Goda, Tomohiko Tamura, Ayako Nakamura-Ishizu, Makoto Suematsu, Atsushi Iwama, Toshio Suda, Keiyo Takubo. Context-dependent modification of PFKFB3 in hematopoietic stem cells promotes anaerobic glycolysis and ensures stress hematopoiesis. eLife 2024, 12 https://doi.org/10.7554/eLife.87674.3
15. Kavit Raval, Neema Jamshidi, Berfin Seyran, Lukasz Salwinski, Raju Pillai, Lixin Yang, Feiyang Ma, Matteo Pellegrini, Juliana Shin, Xia Yang, Slavica Tudzarova. Dysfunctional β-cell longevity in diabetes relies on energy conservation and positive epistasis. 2024https://doi.org/10.1101/2024.03.18.585508
16. Minru Liao, Dahong Yao, Lifeng Wu, Chaodan Luo, Zhiwen Wang, Jin Zhang, Bo Liu. Targeting the Warburg effect: A revisited perspective from molecular mechanisms to traditional and innovative therapeutic strategies in cancer. Acta Pharmaceutica Sinica B 2024, 14 (3) , 953-1008. https://doi.org/10.1016/j.apsb.2023.12.003
17. Shintaro Watanuki, Hiroshi Kobayashi, Yuki Sugiura, Masamichi Yamamoto, Daiki Karigane, Kohei Shiroshita, Yuriko Sorimachi, Shinya Fujita, Takayuki Morikawa, Shuhei Koide, Motohiko Oshima, Akira Nishiyama, Koichi Murakami, Miho Haraguchi, Shinpei Tamaki, Takehiro Yamamoto, Tomohiro Yabushita, Yosuke Tanaka, Go Nagamatsu, Hiroaki Honda, Shinichiro Okamoto, Nobuhito Goda, Tomohiko Tamura, Ayako Nakamura-Ishizu, Makoto Suematsu, Atsushi Iwama, Toshio Suda, Keiyo Takubo. Context-Dependent Modification of PFKFB3 in Hematopoietic Stem Cells Promotes Anaerobic Glycolysis and Ensures Stress Hematopoiesis. 2023https://doi.org/10.7554/eLife.87674.2
18. Sara G. Romeo, Ilaria Secco, Edoardo Schneider, Christina M. Reumiller, Celio X. C. Santos, Anna Zoccarato, Vishal Musale, Aman Pooni, Xiaoke Yin, Konstantinos Theofilatos, Silvia Cellone Trevelin, Lingfang Zeng, Giovanni E. Mann, Varun Pathak, Kevin Harkin, Alan W. Stitt, Reinhold J. Medina, Andriana Margariti, Manuel Mayr, Ajay M. Shah, Mauro Giacca, Anna Zampetaki. Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity. Nature Communications 2023, 14 (1) https://doi.org/10.1038/s41467-023-41326-2
19. Qiuhua Yang, Emily Huo, Yongfeng Cai, Zhidan Zhang, Charles Dong, John M. Asara, Huidong Shi, Qingqing Wei. Myeloid PFKFB3-mediated glycolysis promotes kidney fibrosis. Frontiers in Immunology 2023, 14 https://doi.org/10.3389/fimmu.2023.1259434
20. Yulia Aleksandrova, Margarita Neganova. Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases. International Journal of Molecular Sciences 2023, 24 (19) , 14766. https://doi.org/10.3390/ijms241914766
21. Daniel Jimenez-Blasco, Jesús Agulla, Rebeca Lapresa, Marina Garcia-Macia, Veronica Bobo-Jimenez, Dario Garcia-Rodriguez, Israel Manjarrez-Raza, Emilio Fernandez, Yannick Jeanson, Spiro Khoury, Jean-Charles Portais, Daniel Padro, Pedro Ramos-Cabrer, Peter Carmeliet, Angeles Almeida, Juan P. Bolaños. Weak neuronal glycolysis sustains cognition and organismal fitness. 2023https://doi.org/10.1101/2023.09.02.556016
22. Akanksha Kashyap, Sheikh Mohammad Umar, Arundhathi Dev J. R., Sandeep R. Mathur, Ajay Gogia, Atul Batra, S. V. S. Deo, Chandra Prakash Prasad. Combination of 3PO analog PFK15 and siPFKL efficiently suppresses the migration, colony formation ability, and PFK‐1 activity of triple‐negative breast cancers by reducing the glycolysis. Journal of Cellular Biochemistry 2023, 124 (9) , 1259-1272. https://doi.org/10.1002/jcb.30443
23. Flore Sneyers, Martijn Kerkhofs, Femke Speelman-Rooms, Kirsten Welkenhuyzen, Rita La Rovere, Ahmed Shemy, Arnout Voet, Guy Eelen, Mieke Dewerchin, Stephen W. G. Tait, Bart Ghesquière, Martin D. Bootman, Geert Bultynck. Intracellular BAPTA directly inhibits PFKFB3, thereby impeding mTORC1-driven Mcl-1 translation and killing MCL-1-addicted cancer cells. Cell Death & Disease 2023, 14 (9) https://doi.org/10.1038/s41419-023-06120-4
24. Shiqi Nong, Xiaoyue Han, Yu Xiang, Yuran Qian, Yuhao Wei, Tingyue Zhang, Keyue Tian, Kai Shen, Jing Yang, Xuelei Ma. Metabolic reprogramming in cancer: Mechanisms and therapeutics. MedComm 2023, 4 (2) https://doi.org/10.1002/mco2.218
25. Huiran Yue, Xin Lu. Metabolic reprogramming of the ovarian cancer microenvironment in the development of antiangiogenic resistance. Acta Biochimica et Biophysica Sinica 2023, 72 https://doi.org/10.3724/abbs.2023046
26. Feng Chen, Yi Wu, Yixuan Ma, Honghai Yin, Feijing Su, Rui Huang, Xiaoai Wu, Qian Liu. Synthesis, radiolabeling, and evaluation of 68Ga-labeled aminoquinoxaline derivative as a potent PFKFB3-targeted PET tracer. Frontiers in Chemistry 2023, 11 https://doi.org/10.3389/fchem.2023.1158503
27. Shintaro Watanuki, Hiroshi Kobayashi, Yuki Sugiura, Masamichi Yamamoto, Daiki Karigane, Kohei Shiroshita, Yuriko Sorimachi, Shinya Fujita, Takayuki Morikawa, Shuhei Koide, Motohiko Oshima, Akira Nishiyama, Koichi Murakami, Miho Haraguchi, Shinpei Tamaki, Takehiro Yamamoto, Tomohiro Yabushita, Yosuke Tanaka, Go Nagamatsu, Hiroaki Honda, Shinichiro Okamoto, Nobuhito Goda, Tomohiko Tamura, Ayako Nakamura-Ishizu, Makoto Suematsu, Atsushi Iwama, Toshio Suda, Keiyo Takubo. Context-Dependent Modification of PFKFB3 in Hematopoietic Stem Cells Promotes Anaerobic Glycolysis and Ensures Stress Hematopoiesis. 2023https://doi.org/10.1101/2023.03.16.532898
28. Jie Li, Yan Zhou, Guy Eelen, Qing-tong Zhou, Wen-bo Feng, Viktorija Labroska, Fen-fen Ma, Hui-ping Lu, Mieke Dewerchin, Peter Carmeliet, Ming-wei Wang, De-hua Yang. A high-throughput screening campaign against PFKFB3 identified potential inhibitors with novel scaffolds. Acta Pharmacologica Sinica 2023, 44 (3) , 680-692. https://doi.org/10.1038/s41401-022-00989-1
29. Hao Zhang, Yanghanzhao Wang, Mengdi Qu, Wenqian Li, Dan Wu, Juan P. Cata, Changhong Miao. Neutrophil, neutrophil extracellular traps and endothelial cell dysfunction in sepsis. Clinical and Translational Medicine 2023, 13 (1) https://doi.org/10.1002/ctm2.1170
30. Yuxiu Ye, Jiaqi Liang, Jianglian She, Xiuping Lin, Junfeng Wang, Yonghong Liu, Dehua Yang, Yanhui Tan, Xiaowei Luo, Xuefeng Zhou. Two New Alkaloids and a New Butenolide Derivative from the Beibu Gulf Sponge-Derived Fungus Penicillium sp. SCSIO 41413. Marine Drugs 2023, 21 (1) , 27. https://doi.org/10.3390/md21010027
31. Flore Sneyers, Martijn Kerkhofs, Kirsten Welkenhuyzen, Ahmed Shemy, Arnout Voet, Guy Eelen, Mieke Dewerchin, Stephen Tait, Bart Ghesquière, Martin Bootman, Geert Bultynck, Femke Speelman-Rooms. Intracellular BAPTA directly inhibits PFKFB3, thereby impeding mTORC1-driven Mcl-1 translation and killing Mcl-1-addicted cancer cells. 2022https://doi.org/10.21203/rs.3.rs-1734783/v1
32. Irene Lopez-Fabuel, Marina Garcia-Macia, Costantina Buondelmonte, Olga Burmistrova, Nicolo Bonora, Paula Alonso-Batan, Brenda Morant-Ferrando, Carlos Vicente-Gutierrez, Daniel Jimenez-Blasco, Ruben Quintana-Cabrera, Emilio Fernandez, Jordi Llop, Pedro Ramos-Cabrer, Aseel Sharaireh, Marta Guevara-Ferrer, Lorna Fitzpatrick, Christopher D. Thompton, Tristan R. McKay, Stephan Storch, Diego L. Medina, Sara E. Mole, Peter O. Fedichev, Angeles Almeida, Juan P. Bolaños. Aberrant upregulation of the glycolytic enzyme PFKFB3 in CLN7 neuronal ceroid lipofuscinosis. Nature Communications 2022, 13 (1) https://doi.org/10.1038/s41467-022-28191-1
33. Dominik Awad, Thomas L. Pulliam, Meredith Spradlin, Pham Hong-Anh Cao, Elavarasan Subramani, Tristen V. Tellman, Caroline F. Ribeiro, Hubert Pakula, Jeffrey J. Ackroyd, Mollianne M. Murray, Jenny J. Han, Badrajee Piyarathna, Justin M. Drake, Michael M. Ittmann, Cristian Coarfa, Mary C. Farach-Carson, Massimo Loda, Livia S. Eberlin, Daniel E. Frigo. Adipose triglyceride lipase is regulated by CAMKK2-AMPK signaling and drives advanced prostate cancer. 2022https://doi.org/10.1101/2022.11.02.514910
34. Emmanuel Cruz, Benjamin Bessières, Pierre Magistretti, Cristina M. Alberini. Differential role of neuronal glucose and PFKFB3 in memory formation during development. Glia 2022, 70 (11) , 2207-2231. https://doi.org/10.1002/glia.24248
35. Flore Sneyers, Martijn Kerkhofs, Kirsten Welkenhuyzen, Femke Speelman-Rooms, Ahmed Shemy, Arnout Voet, Guy Eelen, Mieke Dewerchin, Stephen W. Tait, Bart Ghesquière, Martin D. Bootman, Geert Bultynck. Intracellular BAPTA directly inhibits PFKFB3, thereby impeding mTORC1-driven Mcl-1 translation and killing Mcl-1-addicted cancer cells. 2022https://doi.org/10.1101/2022.10.31.512457
36. Parisa Mohammadi, Reza Yarani, Azam Rahimpour, Fatemeh Ranjbarnejad, Joana Mendes Lopes de Melo, Kamran Mansouri. Targeting endothelial cell metabolism in cancerous microenvironment: a new approach for anti-angiogenic therapy. Drug Metabolism Reviews 2022, 54 (4) , 386-400. https://doi.org/10.1080/03602532.2022.2116033
37. Hyo Jung Kim. Minor structural changes, major functional impacts: posttranslational modifications and drug targets. Archives of Pharmacal Research 2022, 45 (10) , 693-703. https://doi.org/10.1007/s12272-022-01409-y
38. Brandon C. Jones, Paula R. Pohlmann, Robert Clarke, Surojeet Sengupta. Treatment against glucose-dependent cancers through metabolic PFKFB3 targeting of glycolytic flux. Cancer and Metastasis Reviews 2022, 41 (2) , 447-458. https://doi.org/10.1007/s10555-022-10027-5
39. Kellen Olszewski, Anthony Barsotti, Xiao-Jiang Feng, Milica Momcilovic, Kevin G. Liu, Ji-In Kim, Koi Morris, Christophe Lamarque, Jack Gaffney, Xuemei Yu, Jeegar P. Patel, Joshua D. Rabinowitz, David B. Shackelford, Masha V. Poyurovsky. Inhibition of glucose transport synergizes with chemical or genetic disruption of mitochondrial metabolism and suppresses TCA cycle-deficient tumors. Cell Chemical Biology 2022, 29 (3) , 423-435.e10. https://doi.org/10.1016/j.chembiol.2021.10.007
40. Jiean Xu, Lina Wang, Qiuhua Yang, Qian Ma, Yaqi Zhou, Yongfeng Cai, Xiaoxiao Mao, Qingen Da, Tammy Lu, Yunchao Su, Zsolt Bagi, Rudolf Lucas, Zhiping Liu, Mei Hong, Kunfu Ouyang, Yuqing Huo. Deficiency of Myeloid Pfkfb3 Protects Mice From Lung Edema and Cardiac Dysfunction in LPS-Induced Endotoxemia. Frontiers in Cardiovascular Medicine 2021, 8 https://doi.org/10.3389/fcvm.2021.745810
41. Selahattin C. Ozcan, Aydan Mutlu, Tugba H. Altunok, Yunus Gurpinar, Aybike Sarioglu, Sabire Guler, Robertino J. Muchut, Alberto A. Iglesias, Serap Celikler, Paul M. Campbell, Abdullah Yalcin. Simultaneous inhibition of PFKFB3 and GLS1 selectively kills KRAS-transformed pancreatic cells. Biochemical and Biophysical Research Communications 2021, 571 , 118-124. https://doi.org/10.1016/j.bbrc.2021.07.070
42. Renée J. H. A. Tillie, Jenny De Bruijn, Javier Perales-Patón, Lieve Temmerman, Yanal Ghosheh, Kim Van Kuijk, Marion J. Gijbels, Peter Carmeliet, Klaus Ley, Julio Saez-Rodriguez, Judith C. Sluimer. Partial Inhibition of the 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase-3 (PFKFB3) Enzyme in Myeloid Cells Does Not Affect Atherosclerosis. Frontiers in Cell and Developmental Biology 2021, 9 https://doi.org/10.3389/fcell.2021.695684
43. Xueyan Sun, Yijiao Peng, Jingduo Zhao, Zhizhong Xie, Xiaoyong Lei, Guotao Tang. Discovery and development of tumor glycolysis rate-limiting enzyme inhibitors. Bioorganic Chemistry 2021, 112 , 104891. https://doi.org/10.1016/j.bioorg.2021.104891
44. Wei Wang, You-Wen Zhang, Shang-Jiu Hu, Wei-Ping Niu, Guo-Ning Zhang, Mei Zhu, Ming-Hua Wang, Fan Zhang, Xue-Mei Li, Ju-Xian Wang. Design, synthesis, and antibacterial evaluation of PFK-158 derivatives as potent agents against drug-resistant bacteria. Bioorganic & Medicinal Chemistry Letters 2021, 41 , 127980. https://doi.org/10.1016/j.bmcl.2021.127980
45. Anahita Abdali, Denisa Baci, Isabella Damiani, Federica Belloni, Carlo De Dominicis, Maria Luisa Gelmi, Alberto Corsini, Stefano Bellosta. In vitro angiogenesis inhibition with selective compounds targeting the key glycolytic enzyme PFKFB3. Pharmacological Research 2021, 168 , 105592. https://doi.org/10.1016/j.phrs.2021.105592
46. Masuko Ushio-Fukai, Dipankar Ash, Sheela Nagarkoti, Eric J. Belin de Chantemèle, David J.R. Fulton, Tohru Fukai. Interplay Between Reactive Oxygen/Reactive Nitrogen Species and Metabolism in Vascular Biology and Disease. Antioxidants & Redox Signaling 2021, 34 (16) , 1319-1354. https://doi.org/10.1089/ars.2020.8161
47. Besa Emini Veseli, Pieter Van Wielendaele, Mirela Delibegovic, Wim Martinet, Guido R. Y. De Meyer. The PFKFB3 Inhibitor AZ67 Inhibits Angiogenesis Independently of Glycolysis Inhibition. International Journal of Molecular Sciences 2021, 22 (11) , 5970. https://doi.org/10.3390/ijms22115970
48. Atul Kumar, Mamta Singh, Dolly Sharma, Vinit Kumar, Reshma Rani. Tumor Metabolism: Focused on Tumor Glycolysis, Progress, and Prospects in Cancer Therapy. 2021, 1-33. https://doi.org/10.1002/0471266949.bmc286
49. Krzysztof Kotowski, Jakub Rosik, Filip Machaj, Stanisław Supplitt, Daniel Wiczew, Karolina Jabłońska, Emilia Wiechec, Saeid Ghavami, Piotr Dzięgiel. Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets. Cancers 2021, 13 (4) , 909. https://doi.org/10.3390/cancers13040909
50. Özgün Babur, Alexander R. Melrose, Jennifer M. Cunliffe, John Klimek, Jiaqing Pang, Anna-Liisa I. Sepp, Jevgenia Zilberman-Rudenko, Samuel Tassi Yunga, Tony Zheng, Iván Parra-Izquierdo, Jessica Minnier, Owen J. T. McCarty, Emek Demir, Ashok P. Reddy, Phillip A. Wilmarth, Larry L. David, Joseph E. Aslan. Phosphoproteomic quantitation and causal analysis reveal pathways in GPVI/ITAM-mediated platelet activation programs. Blood 2020, 136 (20) , 2346-2358. https://doi.org/10.1182/blood.2020005496
51. Irene Lopez-Fabuel, Marina Garcia-Macia, Costantina Buondelmonte, Olga Burmistrova, Nicolo Bonora, Brenda Morant-Ferrando, Paula Alonso-Batan, Carlos Vicente-Gutierrez, Daniel Jimenez-Blasco, Ruben Quintana-Cabrera, Emilio Fernandez, Aseel Sharaireh, Marta Guevara-Ferrer, Lorna Fitzpatrick, Christopher D. Thompton, Tristan R. McKay, Stephan Storch, Diego L. Medina, Sara E. Mole, Peter O. Fedichev, Angeles Almeida, Juan P. Bolaños. Mitochondrial collapse links PFKFB3-promoted glycolysis with CLN7/MFSD8 neuronal ceroid lipofuscinosis pathogenesis. 2020https://doi.org/10.1101/2020.10.20.345314
52. Yinhu Wang, Chen Qu, Tingting Liu, Chunhui Wang. PFKFB3 inhibitors as potential anticancer agents: Mechanisms of action, current developments, and structure-activity relationships. European Journal of Medicinal Chemistry 2020, 203 , 112612. https://doi.org/10.1016/j.ejmech.2020.112612
53. Besa Emini Veseli, Paola Perrotta, Pieter Van Wielendaele, Anne‐Marie Lambeir, Anahita Abdali, Stefano Bellosta, Giovanni Monaco, Geert Bultynck, Wim Martinet, Guido R. Y. De Meyer. Small molecule 3PO inhibits glycolysis but does not bind to 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase‐3 (PFKFB3). FEBS Letters 2020, 594 (18) , 3067-3075. https://doi.org/10.1002/1873-3468.13878
54. Qian Cai, Wei Zhou. Ullmann‐Ma Reaction: Development, Scope and Applications in Organic Synthesis †. Chinese Journal of Chemistry 2020, 38 (8) , 879-893. https://doi.org/10.1002/cjoc.202000075
55. Paola Perrotta, Bieke Van der Veken, Pieter Van Der Veken, Isabel Pintelon, Laurence Roosens, Elias Adriaenssens, Vincent Timmerman, Pieter-Jan Guns, Guido R.Y. De Meyer, Wim Martinet. Partial Inhibition of Glycolysis Reduces Atherogenesis Independent of Intraplaque Neovascularization in Mice. Arteriosclerosis, Thrombosis, and Vascular Biology 2020, 40 (5) , 1168-1181. https://doi.org/10.1161/ATVBAHA.119.313692
56. Yuan Guan, Xinyu Chen, Manhong Wu, Wan Zhu, Ahmed Arslan, Saori Takeda, Mindie H. Nguyen, Ravindra Majeti, Dan Thomas, Ming Zheng, Gary Peltz. The phosphatidylethanolamine biosynthesis pathway provides a new target for cancer chemotherapy. Journal of Hepatology 2020, 72 (4) , 746-760. https://doi.org/10.1016/j.jhep.2019.11.007
57. Nina E. Murugina, Anna S. Budikhina, Yulia A. Dagil, Polina V. Maximchik, Lyudmila S. Balyasova, Vladimir V. Murugin, Mikhail V. Melnikov, Viktoriya S. Sharova, Anna M. Nikolaeva, Georgy Z. Chkadua, Boris V. Pinegin, Mikhail V. Pashenkov. Glycolytic reprogramming of macrophages activated by NOD1 and TLR4 agonists: No association with proinflammatory cytokine production in normoxia. Journal of Biological Chemistry 2020, 295 (10) , 3099-3114. https://doi.org/10.1074/jbc.RA119.010589
58. Olga Burmistrova, Ana Olias-Arjona, Rebeca Lapresa, Daniel Jimenez-Blasco, Tatiana Eremeeva, Dmitry Shishov, Sergei Romanov, Kristina Zakurdaeva, Angeles Almeida, Peter O. Fedichev, Juan P. Bolaños. Targeting PFKFB3 alleviates cerebral ischemia-reperfusion injury in mice. Scientific Reports 2019, 9 (1) https://doi.org/10.1038/s41598-019-48196-z
59. Helena Macut, Xiao Hu, Delia Tarantino, Ettore Gilardoni, Francesca Clerici, Luca Regazzoni, Alessandro Contini, Sara Pellegrino, Maria Luisa Gelmi. Tuning PFKFB3 Bisphosphatase Activity Through Allosteric Interference. Scientific Reports 2019, 9 (1) https://doi.org/10.1038/s41598-019-56708-0
60. Jun Wang, Xiaojuan Li, Zhaoming Xiao, Yu Wang, Yuefu Han, Jun Li, Weian Zhu, Qu Leng, Yuehui Wen, Xinqiao Wen. MicroRNA‐488 inhibits proliferation and glycolysis in human prostate cancer cells by regulating PFKFB3. FEBS Open Bio 2019, 9 (10) , 1798-1807. https://doi.org/10.1002/2211-5463.12718
61. Yapeng Cao, Xiaoyu Zhang, Lina Wang, Qiuhua Yang, Qian Ma, Jiean Xu, Jingjing Wang, Laszlo Kovacs, Ramon J. Ayon, Zhiping Liu, Min Zhang, Yaqi Zhou, Xianqiu Zeng, Yiming Xu, Yong Wang, David J. Fulton, Neal L. Weintraub, Rudolf Lucas, Zheng Dong, Jason X.-J. Yuan, Jennifer C. Sullivan, Louise Meadows, Scott A. Barman, Chaodong Wu, Junmin Quan, Mei Hong, Yunchao Su, Yuqing Huo. PFKFB3-mediated endothelial glycolysis promotes pulmonary hypertension. Proceedings of the National Academy of Sciences 2019, 116 (27) , 13394-13403. https://doi.org/10.1073/pnas.1821401116
62. Nicolas Boutard, Arkadiusz Białas, Aleksandra Sabiniarz, Paweł Guzik, Katarzyna Banaszak, Artur Biela, Marcin Bień, Anna Buda, Barbara Bugaj, Ewelina Cieluch, Anna Cierpich, Łukasz Dudek, Hans-Michael Eggenweiler, Joanna Fogt, Monika Gaik, Andrzej Gondela, Krzysztof Jakubiec, Mirek Jurzak, Agata Kitlińska, Piotr Kowalczyk, Maciej Kujawa, Katarzyna Kwiecińska, Marcin Leś, Ralph Lindemann, Monika Maciuszek, Maciej Mikulski, Paulina Niedziejko, Alicja Obara, Henryk Pawlik, Tomasz Rzymski, Magdalena Sieprawska-Lupa, Marta Sowińska, Joanna Szeremeta-Spisak, Agata Stachowicz, Mateusz M. Tomczyk, Katarzyna Wiklik, Łukasz Włoszczak, Sylwia Ziemiańska, Adrian Zarębski, Krzysztof Brzózka, Mateusz Nowak, Charles-Henry Fabritius. Synthesis of amide and sulfonamide substituted N-aryl 6-aminoquinoxalines as PFKFB3 inhibitors with improved physicochemical properties. Bioorganic & Medicinal Chemistry Letters 2019, 29 (4) , 646-653. https://doi.org/10.1016/j.bmcl.2018.12.034
63. Mei Yi, Yuanyuan Ban, Yixin Tan, Wei Xiong, Guiyuan Li, Bo Xiang. 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 and 4: A pair of valves for fine-tuning of glucose metabolism in human cancer. Molecular Metabolism 2019, 20 , 1-13. https://doi.org/10.1016/j.molmet.2018.11.013
64. Olga Burmistrova, Ana Olias-Arjona, Tatiana Eremeeva, Dmitry Shishov, Kristina Zakurdaeva, Angeles Almeida, Peter O. Fedichev, Juan P. Bolaños. Targeting PFKFB3 alleviates cerebral ischemia-reperfusion injury in mice. 2019https://doi.org/10.1101/518092
65. Nicolas Boutard, Arkadiusz Białas, Aleksandra Sabiniarz, Paweł Guzik, Katarzyna Banaszak, Artur Biela, Marcin Bień, Anna Buda, Barbara Bugaj, Ewelina Cieluch, Anna Cierpich, Łukasz Dudek, Hans‐Michael Eggenweiler, Joanna Fogt, Monika Gaik, Andrzej Gondela, Krzysztof Jakubiec, Mirek Jurzak, Agata Kitlińska, Piotr Kowalczyk, Maciej Kujawa, Katarzyna Kwiecińska, Marcin Leś, Ralph Lindemann, Monika Maciuszek, Maciej Mikulski, Paulina Niedziejko, Alicja Obara, Henryk Pawlik, Tomasz Rzymski, Magdalena Sieprawska‐Lupa, Marta Sowińska, Joanna Szeremeta‐Spisak, Agata Stachowicz, Mateusz M. Tomczyk, Katarzyna Wiklik, Łukasz Włoszczak, Sylwia Ziemiańska, Adrian Zarębski, Krzysztof Brzózka, Mateusz Nowak, Charles‐Henry Fabritius. Discovery and Structure–Activity Relationships of N ‐Aryl 6‐Aminoquinoxalines as Potent PFKFB3 Kinase Inhibitors. ChemMedChem 2019, 14 (1) , 169-181. https://doi.org/10.1002/cmdc.201800569
66. Paola Perrotta, Besa Emini Veseli, Bieke Van der Veken, Lynn Roth, Wim Martinet, Guido R.Y. De Meyer. Pharmacological strategies to inhibit intra-plaque angiogenesis in atherosclerosis. Vascular Pharmacology 2019, 112 , 72-78. https://doi.org/10.1016/j.vph.2018.06.014
67. Nina M. S. Gustafsson, Katarina Färnegårdh, Nadilly Bonagas, Anna Huguet Ninou, Petra Groth, Elisee Wiita, Mattias Jönsson, Kenth Hallberg, Jemina Lehto, Rosa Pennisi, Jessica Martinsson, Carina Norström, Jessica Hollers, Johan Schultz, Martin Andersson, Natalia Markova, Petra Marttila, Baek Kim, Martin Norin, Thomas Olin, Thomas Helleday. Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination. Nature Communications 2018, 9 (1) https://doi.org/10.1038/s41467-018-06287-x
68. Yinfeng Bao, Lu Zhou, Duoqian Dai, Xiaohong Zhu, Yanqiu Hu, Yaping Qiu. Discover potential inhibitors for PFKFB3 using 3D-QSAR, virtual screening, molecular docking and molecular dynamics simulation. Journal of Receptors and Signal Transduction 2018, 38 (5-6) , 413-431. https://doi.org/10.1080/10799893.2018.1564150
69. Roland W. Bürli, Huijun Wei, Glen Ernst, Abigail Mariga, Ian M. Hardern, Kara Herlihy, Alan J. Cross, Steven S. Wesolowski, Hongming Chen, Ronald D.G. McKay, Daniel R. Weinberger, Nicholas J. Brandon, James C. Barrow. Novel inhibitors of As(III) S-adenosylmethionine methyltransferase (AS3MT) identified by virtual screening. Bioorganic & Medicinal Chemistry Letters 2018, 28 (19) , 3231-3235. https://doi.org/10.1016/j.bmcl.2018.08.012
70. Ramon Bartrons, Ana Rodríguez-García, Helga Simon-Molas, Esther Castaño, Anna Manzano, Àurea Navarro-Sabaté. The potential utility of PFKFB3 as a therapeutic target. Expert Opinion on Therapeutic Targets 2018, 22 (8) , 659-674. https://doi.org/10.1080/14728222.2018.1498082
71. Guy Eelen, Pauline de Zeeuw, Lucas Treps, Ulrike Harjes, Brian W. Wong, Peter Carmeliet. Endothelial Cell Metabolism. Physiological Reviews 2018, 98 (1) , 3-58. https://doi.org/10.1152/physrev.00001.2017
72. Stephen A. St-Gallay, Neil Bennett, Susan E. Critchlow, Nicola Curtis, Gareth Davies, Judit Debreczeni, Nicola Evans, Ian Hardern, Geoff Holdgate, Neil P. Jones, Lindsey Leach, Sarita Maman, Sheila McLoughlin, Marian Preston, Laurent Rigoreau, Andrew Thomas, Andrew P. Turnbull, Graeme Walker, Jarrod Walsh, Richard A. Ward, Ed Wheatley, Jon Winter-Holt. A High-Throughput Screening Triage Workflow to Authenticate a Novel Series of PFKFB3 Inhibitors. SLAS Discovery 2018, 23 (1) , 11-22. https://doi.org/10.1177/2472555217732289
73. Nihed Draoui, Pauline de Zeeuw, Peter Carmeliet. Angiogenesis revisited from a metabolic perspective: role and therapeutic implications of endothelial cell metabolism. Open Biology 2017, 7 (12) , 170219. https://doi.org/10.1098/rsob.170219
74. Xin Zheng, Han Han, Guang‐Ping Liu, Yan‐Xiu Ma, Ruo‐Lang Pan, Ling‐Jie Sang, Rui‐Hua Li, Luo‐Jia Yang, Jeffrey R Marks, Wenqi Wang, Aifu Lin. Lnc RNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism. The EMBO Journal 2017, 36 (22) , 3325-3335. https://doi.org/10.15252/embj.201797609
75. Nusrat Chowdhury, Imran Vhora, Ketan Patel, Ravi Doddapaneni, Arindam Mondal, Mandip Singh. Liposomes co-Loaded with 6-Phosphofructo-2-Kinase/Fructose-2, 6-Biphosphatase 3 (PFKFB3) shRNA Plasmid and Docetaxel for the Treatment of non-small Cell Lung Cancer. Pharmaceutical Research 2017, 34 (11) , 2371-2384. https://doi.org/10.1007/s11095-017-2244-x
76. Peter J. Lindsay-Scott, Peter T. Gallagher. Synthesis of heterocycles from arylacetonitriles: Powerful tools for medicinal chemists. Tetrahedron Letters 2017, 58 (27) , 2629-2635. https://doi.org/10.1016/j.tetlet.2017.05.089
77. John P. Harrelson, Michael W. Lee. Expanding the view of breast cancer metabolism: Promising molecular targets and therapeutic opportunities. Pharmacology & Therapeutics 2016, 167 , 60-73. https://doi.org/10.1016/j.pharmthera.2016.07.014
78. Michael A. Reid, Xazmin H. Lowman, Min Pan, Thai Q. Tran, Marc O. Warmoes, Mari B. Ishak Gabra, Ying Yang, Jason W. Locasale, Mei Kong. IKKβ promotes metabolic adaptation to glutamine deprivation via phosphorylation and inhibition of PFKFB3. Genes & Development 2016, 30 (16) , 1837-1851. https://doi.org/10.1101/gad.287235.116
79. Manjunatha Vishwanath, Koilpitchai Sivamuthuraman, Venkitasamy Kesavan. An efficient construction of N,N-bicyclic pyrazolidinones comprising enaminonitriles via asymmetric [3+2] cycloaddition. Chemical Communications 2016, 52 (83) , 12314-12317. https://doi.org/10.1039/C6CC05304A
80. Thavaraj Vivekanand, Thiruvalluvan Sandhya, Perumal Vinoth, Subbiah Nagarajan, C. Uma Maheswari, Vellaisamy Sridharan. N-(2-Aminobenzylidene)-4-methylanilines—stable and cheap alternate for 2-aminobenzaldehydes: concise synthesis of 3-unsubstituted-2-aroylindoles. Tetrahedron Letters 2015, 56 (38) , 5291-5294. https://doi.org/10.1016/j.tetlet.2015.07.073