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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Perspective

Targeting T Cell Metabolism as a Novel Approach for Treatment of MS: With a Focus on PFKFB3 Inhibitors

Author(s): Mahsa Eshkevar Vakili, Fateme Nezhad Shah Mohammadi, Mohammad Reza Ataollahi, Keivan Shams, Kari K. Eklund, Gholamreza Daryabor and Kurosh Kalantar*

Volume 23, Issue 4, 2023

Published on: 14 November, 2022

Page: [417 - 422] Pages: 6

DOI: 10.2174/1871530322666220921160930

Abstract

Multiple sclerosis (MS) is one of the organ-specific autoimmune diseases in which immune cells invade the neurons in the central nervous system (CNS) due to loss of tolerance to self-antigens. Consequently, inflammation and demyelination occur in the central nervous system. The pathogenesis of MS is not completely understood. However, it seems that T cells, especially Th17 cells, have an important role in disease development. In recent years, studies on the manipulation of metabolic pathways with therapeutic targets have received increasing attention and have had promising results in some diseases, such as cancers. Glycolysis is a central metabolic pathway and plays an important role in the differentiation of T CD4+ cells to their subsets, especially Th17 cells. This suggests that manipulation of glycolysis, for example, using appropriate safe inhibitors of this pathway can represent a means to affect the differentiation of T CD4+, thus reducing inflammation and disease activity in MS patients. Hence, in this study, we aimed to discuss evidence showing that using inhibitors of 6-phosphofructo-2- kinase/fructose-2,6-biphosphatase 3(PFKFB3) as the main regulator of glycolysis may exert beneficial therapeutic effects on MS patients.

Keywords: Multiple sclerosis, autoimmunity, inflammation, TH17 cells, glycolysis, PFKB3

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[1]
Qiu, R.; Zhou, L.; Ma, Y.; Zhou, L.; Liang, T.; Shi, L.; Long, J.; Yuan, D. Regulatory T cell plasticity and stability and autoimmune diseases. Clin. Rev. Allergy Immunol., 2020, 58(1), 52-70.
[http://dx.doi.org/10.1007/s12016-018-8721-0] [PMID: 30449014]
[2]
Khan, H.; Sureda, A.; Belwal, T.; Çetinkaya, S.; Süntar, İ.; Tejada, S.; Devkota, H.P.; Ullah, H.; Aschner, M. Polyphenols in the treatment of autoimmune diseases. Autoimmun. Rev., 2019, 18(7), 647-657.
[http://dx.doi.org/10.1016/j.autrev.2019.05.001] [PMID: 31059841]
[3]
Walton, C.; King, R.; Rechtman, L.; Kaye, W.; Leray, E.; Marrie, R.A.; Robertson, N.; La Rocca, N.; Uitdehaag, B.; van der Mei, I.; Wallin, M.; Helme, A.; Angood Napier, C.; Rijke, N.; Baneke, P. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult. Scler., 2020, 26(14), 1816-1821.
[http://dx.doi.org/10.1177/1352458520970841] [PMID: 33174475]
[4]
Lopes Pinheiro, M.A.; Kooij, G.; Mizee, M.R.; Kamermans, A.; Enzmann, G.; Lyck, R.; Schwaninger, M.; Engelhardt, B.; de Vries, H.E. Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke. Biochim. Biophys. Acta Mol. Basis Dis., 2016, 1862(3), 461-471.
[http://dx.doi.org/10.1016/j.bbadis.2015.10.018]
[5]
Vojdani, A. A potential link between environmental triggers and autoimmunity. Autoimmuneclis diseases, 2014, 2014
[http://dx.doi.org/10.1155/2014/437231]
[6]
Wang, L.; Wang, F.S.; Gershwin, M.E. Human autoimmune diseases: A comprehensive update. J. Intern. Med., 2015, 278(4), 369-395.
[http://dx.doi.org/10.1111/joim.12395] [PMID: 26212387]
[7]
Nourbakhsh, B.; Mowry, E.M. Multiple sclerosis risk factors and pathogenesis. Continuum (Minneap. Minn.), 2019, 25(3), 596-610.
[http://dx.doi.org/10.1212/CON.0000000000000725] [PMID: 31162307]
[8]
Lovett-Racke, A.E.; Yang, Y.; Racke, M.K. Th1 versus Th17: Are T cell cytokines relevant in multiple sclerosis? Biochim. Biophys. Acta Mol. Basis Dis., 2011, 1812(2), 246-251.
[http://dx.doi.org/10.1016/j.bbadis.2010.05.012] [PMID: 20600875]
[9]
Dhaiban, S.; Al-Ani, M.; Elemam, N.M.; Al-Aawad, M.H.; Al-Rawi, Z.; Maghazachi, A.A. Role of peripheral immune cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Sci, 2021, 3(1), 12.
[http://dx.doi.org/10.3390/sci3010012]
[10]
Prajeeth, C.K.; Löhr, K.; Floess, S.; Zimmermann, J.; Ulrich, R.; Gudi, V.; Beineke, A.; Baumgärtner, W.; Müller, M.; Huehn, J.; Stangel, M. Effector molecules released by Th1 but not Th17 cells drive an M1 response in microglia. Brain Behav. Immun., 2014, 37, 248-259.
[http://dx.doi.org/10.1016/j.bbi.2014.01.001] [PMID: 24412213]
[11]
Tzartos, J.S.; Friese, M.A.; Craner, M.J.; Palace, J.; Newcombe, J.; Esiri, M.M.; Fugger, L. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am. J. Pathol., 2008, 172(1), 146-155.
[http://dx.doi.org/10.2353/ajpath.2008.070690] [PMID: 18156204]
[12]
Reboldi, A.; Coisne, C.; Baumjohann, D.; Benvenuto, F.; Bottinelli, D.; Lira, S.; Uccelli, A.; Lanzavecchia, A.; Engelhardt, B.; Sallusto, F. C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat. Immunol., 2009, 10(5), 514-523.
[http://dx.doi.org/10.1038/ni.1716] [PMID: 19305396]
[13]
Korn, T.; Bettelli, E.; Oukka, M.; Kuchroo, V.K. IL-17 and Th17 cells. Annu. Rev. Immunol., 2009, 27(1), 485-517.
[http://dx.doi.org/10.1146/annurev.immunol.021908.132710] [PMID: 19132915]
[14]
Moser, T.; Akgün, K.; Proschmann, U.; Sellner, J.; Ziemssen, T. The role of TH17 cells in multiple sclerosis: Therapeutic implications. Autoimmun. Rev., 2020, 19(10), 102647.
[http://dx.doi.org/10.1016/j.autrev.2020.102647] [PMID: 32801039]
[15]
Li, Y.F.; Zhang, S.X.; Ma, X.W.; Xue, Y.L.; Gao, C.; Li, X.Y. Levels of peripheral Th17 cells and serum Th17-related cytokines in patients with multiple sclerosis: A meta-analysis. Mult. Scler. Relat. Disord., 2017, 18, 20-25.
[http://dx.doi.org/10.1016/j.msard.2017.09.003] [PMID: 29141810]
[16]
El-Behi, M.; Ciric, B.; Dai, H.; Yan, Y.; Cullimore, M.; Safavi, F.; Zhang, G.X.; Dittel, B.N.; Rostami, A. The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat. Immunol., 2011, 12(6), 568-575.
[http://dx.doi.org/10.1038/ni.2031] [PMID: 21516111]
[17]
Langrish, C.L.; Chen, Y.; Blumenschein, W.M.; Mattson, J.; Basham, B.; Sedgwick, J.D.; McClanahan, T.; Kastelein, R.A.; Cua, D.J. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med., 2005, 201(2), 233-240.
[http://dx.doi.org/10.1084/jem.20041257] [PMID: 15657292]
[18]
Ivanov, I.I.; McKenzie, B.S.; Zhou, L.; Tadokoro, C.E.; Lepelley, A.; Lafaille, J.J.; Cua, D.J.; Littman, D.R. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell, 2006, 126(6), 1121-1133.
[http://dx.doi.org/10.1016/j.cell.2006.07.035] [PMID: 16990136]
[19]
Pearce, E.L.; Pearce, E.J. Metabolic pathways in immune cell activation and quiescence. Immunity, 2013, 38(4), 633-643.
[http://dx.doi.org/10.1016/j.immuni.2013.04.005] [PMID: 23601682]
[20]
Shi, L.Z.; Wang, R.; Huang, G.; Vogel, P.; Neale, G.; Green, D.R.; Chi, H. HIF1α-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and treg cells. J. Exp. Med., 2011, 208(7), 1367-1376.
[http://dx.doi.org/10.1084/jem.20110278] [PMID: 21708926]
[21]
De Riccardis, L.; Rizzello, A.; Ferramosca, A.; Urso, E.; De Robertis, F.; Danieli, A.; Giudetti, A.M.; Trianni, G.; Zara, V.; Maffia, M. Bioenergetics profile of CD4 + T cells in relapsing remitting multiple sclerosis subjects. J. Biotechnol., 2015, 202, 31-39.
[http://dx.doi.org/10.1016/j.jbiotec.2015.02.015] [PMID: 25701681]
[22]
Kunkl, M.; Sambucci, M.; Ruggieri, S.; Amormino, C.; Tortorella, C.; Gasperini, C.; Battistini, L.; Tuosto, L. CD28 autonomous signaling up-regulates C-Myc expression and promotes glycolysis enabling inflammatory T cell responses in multiple sclerosis. Cells, 2019, 8(6), 575.
[http://dx.doi.org/10.3390/cells8060575] [PMID: 31212712]
[23]
Tavassolifar, M.J.; Moghadasi, A.N.; Esmaeili, B.; Sadatpour, O.; Vodjgani, M.; Izad, M. Redox imbalance in CD4+ T cells of relapsing-remitting multiple sclerosis patients. Oxid. Med. Cell. Longev., 2020, 2020, 8860813.
[24]
Gonzalo, H.; Nogueras, L.; Gil-Sánchez, A.; Hervás, J.V.; Valcheva, P.; González-Mingot, C.; Martin-Gari, M.; Canudes, M.; Peralta, S.; Solana, M.J.; Pamplona, R.; Portero-Otin, M.; Boada, J.; Serrano, J.C.E.; Brieva, L. Impairment of mitochondrial redox status in peripheral lymphocytes of multiple sclerosis patients. Front. Neurosci., 2019, 13, 938.
[http://dx.doi.org/10.3389/fnins.2019.00938] [PMID: 31551694]
[25]
De Rasmo, D.; Ferretta, A.; Russo, S.; Ruggieri, M.; Lasorella, P.; Paolicelli, D.; Trojano, M.; Signorile, A. PBMC of multiple sclerosis patients show deregulation of OPA1 processing associated with increased ROS and PHB2 protein levels. Biomedicines, 2020, 8(4), 85.
[http://dx.doi.org/10.3390/biomedicines8040085] [PMID: 32290388]
[26]
La Rocca, C.; Carbone, F.; De Rosa, V.; Colamatteo, A.; Galgani, M.; Perna, F.; Lanzillo, R.; Brescia Morra, V.; Orefice, G.; Cerillo, I.; Florio, C.; Maniscalco, G.T.; Salvetti, M.; Centonze, D.; Uccelli, A.; Longobardi, S.; Visconti, A.; Matarese, G. Immunometabolic profiling of T cells from patients with relapsing-remitting multiple sclerosis reveals an impairment in glycolysis and mitochondrial respiration. Metabolism, 2017, 77, 39-46.
[http://dx.doi.org/10.1016/j.metabol.2017.08.011] [PMID: 29132538]
[27]
Angiari, S.; O’Neill, L.A. Dimethyl fumarate: Targeting glycolysis to treat MS. Cell Res., 2018, 28(6), 613-615.
[http://dx.doi.org/10.1038/s41422-018-0045-3] [PMID: 29844579]
[28]
Kornberg, M.D.; Bhargava, P.; Kim, P.M.; Putluri, V.; Snowman, A.M.; Putluri, N.; Calabresi, P.A.; Snyder, S.H. Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity. Science, 2018, 360(6387), 449-453.
[http://dx.doi.org/10.1126/science.aan4665] [PMID: 29599194]
[29]
Kono, M.; Yoshida, N.; Maeda, K.; Suárez-Fueyo, A.; Kyttaris, V.C.; Tsokos, G.C. Glutaminase 1 inhibition reduces glycolysis and ameliorates lupus‐like disease in MRL/lpr mice and experimental autoimmune encephalomyelitis. Arthritis Rheumatol., 2019, 71(11), 1869-1878.
[http://dx.doi.org/10.1002/art.41019] [PMID: 31233276]
[30]
Qian, Y.; Wang, X.; Chen, X. Inhibitors of glucose transport and glycolysis as novel anticancer therapeutics. World J. Transl. Med., 2014, 3(2), 37-57.
[http://dx.doi.org/10.5528/wjtm.v3.i2.37]
[31]
Lu, L.; Chen, Y.; Zhu, Y. The molecular basis of targeting PFKFB3 as a therapeutic strategy against cancer. Oncotarget, 2017, 8(37), 62793-62802.
[http://dx.doi.org/10.18632/oncotarget.19513] [PMID: 28977989]
[32]
Wang, Y.; Qu, C.; Liu, T.; Wang, C. PFKFB3 inhibitors as potential anticancer agents: Mechanisms of action, current developments, and structure-activity relationships. Eur. J. Med. Chem., 2020, 203, 112612.
[http://dx.doi.org/10.1016/j.ejmech.2020.112612] [PMID: 32679452]
[33]
Yi, M.; Ban, Y.; Tan, Y.; Xiong, W.; Li, G.; Xiang, B. 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 and 4: A pair of valves for fine-tuning of glucose metabolism in human cancer. Mol. Metab., 2019, 20, 1-13.
[http://dx.doi.org/10.1016/j.molmet.2018.11.013] [PMID: 30553771]
[34]
Minchenko, A.; Leshchinsky, I.; Opentanova, I.; Sang, N.; Srinivas, V.; Armstead, V.; Caro, J. Hypoxia-inducible factor-1-mediated expression of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKF B3) gene. J. Biol. Chem., 2002, 277(8), 6183-6187.
[http://dx.doi.org/10.1074/jbc.M110978200] [PMID: 11744734]
[35]
Emini Veseli, B.; Van Wielendaele, P.; Delibegovic, M.; Martinet, W.; De Meyer, G.R.Y. The PFKFB3 inhibitor AZ67 inhibits angiogenesis independently of glycolysis inhibition. Int. J. Mol. Sci., 2021, 22(11), 5970.
[http://dx.doi.org/10.3390/ijms22115970] [PMID: 34073144]
[36]
Manzano, A.; Rosa, J.L.; Ventura, F.; Pérez, J.X.; Nadal, M.; Estivill, X.; Ambrosio, S.; Gil, J.; Bartrons, R. Molecular cloning, expression, and chromosomal localization of a ubiquitously expressed human 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene (PFKFB3). Cytogenet. Genome Res., 1998, 83(3-4), 214-217.
[http://dx.doi.org/10.1159/000015181] [PMID: 10072580]
[37]
Mahlknecht, U.; Chesney, J.; Hoelzer, D.; Bucala, R. Cloning and chromosomal characterization of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 gene (PFKFB3, iPFK2). Int. J. Oncol., 2003, 23(4), 883-891.
[http://dx.doi.org/10.3892/ijo.23.4.883] [PMID: 12963966]
[38]
Halder, S.K.; Milner, R. Hypoxia in multiple sclerosis; is it the chicken or the egg? Brain, 2021, 144(2), 402-410.
[http://dx.doi.org/10.1093/brain/awaa427] [PMID: 33351069]
[39]
Obach, M.; Navarro-Sabaté, À.; Caro, J.; Kong, X.; Duran, J.; Gómez, M.; Perales, J.C.; Ventura, F.; Rosa, J.L.; Bartrons, R. 6-Phosphofructo-2-kinase (PFKFB3) gene promoter contains hypoxia-inducible factor-1 binding sites necessary for transactivation in response to hypoxia. J. Biol. Chem., 2004, 279(51), 53562-53570.
[http://dx.doi.org/10.1074/jbc.M406096200] [PMID: 15466858]
[40]
Rider, M.H.; Bertrand, L.; Vertommen, D.; Michels, P.A.; Rousseau, G.G.; Hue, L. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: Head-to-head with a bifunctional enzyme that controls glycolysis. Biochem. J., 2004, 381(3), 561-579.
[http://dx.doi.org/10.1042/BJ20040752] [PMID: 15170386]
[41]
Kim, S.G.; Manes, N.P.; El-Maghrabi, M.R.; Lee, Y.H. Crystal structure of the hypoxia-inducible form of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). J. Biol. Chem., 2006, 281(5), 2939-2944.
[http://dx.doi.org/10.1074/jbc.M511019200] [PMID: 16316985]
[42]
O’Neal, J.; Clem, A.; Reynolds, L.; Dougherty, S.; Imbert-Fernandez, Y.; Telang, S.; Chesney, J.; Clem, B.F. Inhibition of 6-phosphofructo-2-kinase (PFKFB3) suppresses glucose metabolism and the growth of HER2+ breast cancer. Breast Cancer Res. Treat., 2016, 160(1), 29-40.
[http://dx.doi.org/10.1007/s10549-016-3968-8] [PMID: 27613609]
[43]
Kessler, R.; Bleichert, F.; Warnke, J.P.; Eschrich, K. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) is up-regulated in high-grade astrocytomas. J. Neurooncol., 2008, 86(3), 257-264.
[http://dx.doi.org/10.1007/s11060-007-9471-7] [PMID: 17805487]
[44]
Nomoto, H.; Pei, L.; Montemurro, C.; Rosenberger, M.; Furterer, A.; Coppola, G.; Nadel, B.; Pellegrini, M.; Gurlo, T.; Butler, P.C.; Tudzarova, S. Activation of the HIF1α/PFKFB3 stress response pathway in beta cells in type 1 diabetes. Diabetologia, 2020, 63(1), 149-161.
[http://dx.doi.org/10.1007/s00125-019-05030-5] [PMID: 31720731]
[45]
La Belle Flynn, A.; Calhoun, B.C.; Sharma, A.; Chang, J.C.; Almasan, A.; Schiemann, W.P. Autophagy inhibition elicits emergence from metastatic dormancy by inducing and stabilizing Pfkfb3 expression. Nat. Commun., 2019, 10(1), 3668.
[http://dx.doi.org/10.1038/s41467-019-11640-9] [PMID: 31413316]
[46]
Li, X.; Liu, J.; Qian, L.; Ke, H.; Yao, C.; Tian, W.; Liu, Y.; Zhang, J. Expression of PFKFB3 and Ki67 in lung adenocarcinomas and targeting PFKFB3 as a therapeutic strategy. Mol. Cell. Biochem., 2018, 445(1-2), 123-134.
[http://dx.doi.org/10.1007/s11010-017-3258-8] [PMID: 29327288]
[47]
Martins, C.P.; New, L.A.; O’Connor, E.C.; Previte, D.M.; Cargill, K.R.; Tse, I.L. Sims- Lucas, S.; Piganelli, J.D. Glycolysis inhibition induces functional and metabolic exhaustion of CD4+ T cells in type 1 diabetes. Front. Immunol., 2021, 12, 669456.
[http://dx.doi.org/10.3389/fimmu.2021.669456] [PMID: 34163475]
[48]
Peng, F.; Li, Q.; Sun, J.Y.; Luo, Y.; Chen, M.; Bao, Y. PFKFB3 is involved in breast cancer proliferation, migration, invasion and angiogenesis. Int. J. Oncol., 2018, 52(3), 945-954.
[http://dx.doi.org/10.3892/ijo.2018.4257] [PMID: 29393396]
[49]
De Oliveira, T.; Goldhardt, T.; Edelmann, M.; Rogge, T.; Rauch, K.; Kyuchukov, N.D.; Menck, K.; Bleckmann, A.; Kalucka, J.; Khan, S.; Gaedcke, J.; Haubrock, M.; Beissbarth, T.; Bohnenberger, H.; Planque, M.; Fendt, S.M.; Ackermann, L.; Ghadimi, M.; Conradi, L.C. Effects of the novel PFKFB3 inhibitor KAN0438757 on colorectal cancer cells and its systemic toxicity evaluation in vivo. Cancers (Basel), 2021, 13(5), 1011.
[http://dx.doi.org/10.3390/cancers13051011] [PMID: 33671096]
[50]
Xing, J.; Jia, Z.; Xu, Y.; Chen, M.; Yang, Z.; Chen, Y.; Han, Y. KLF9 (kruppel like factor 9) induced PFKFB3 (6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3) downregulation inhibits the proliferation, metastasis and aerobic glycolysis of cutaneous squamous cell carcinoma cells. Bioengineered, 2021, 12(1), 7563-7576.
[http://dx.doi.org/10.1080/21655979.2021.1980644] [PMID: 34612136]
[51]
Yang, Z.; Shen, Y.; Oishi, H.; Matteson, E.L.; Tian, L.; Goronzy, J.J.; Weyand, C.M. Restoring oxidant signaling suppresses proarthritogenic T cell effector functions in rheumatoid arthritis. Sci. Transl. Med., 2016, 8(331), 331-338.
[http://dx.doi.org/10.1126/scitranslmed.aad7151]
[52]
Movafagh, S.; Crook, S.; Vo, K. Regulation of hypoxia-inducible factor-1a by reactive oxygen species: New developments in an old debate. J. Cell. Biochem., 2015, 116(5), 696-703.
[http://dx.doi.org/10.1002/jcb.25074] [PMID: 25546605]
[53]
Dang, E.V.; Barbi, J.; Yang, H.Y.; Jinasena, D.; Yu, H.; Zheng, Y.; Bordman, Z.; Fu, J.; Kim, Y.; Yen, H.R.; Luo, W.; Zeller, K.; Shimoda, L.; Topalian, S.L.; Semenza, G.L.; Dang, C.V.; Pardoll, D.M.; Pan, F. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell, 2011, 146(5), 772-784.
[http://dx.doi.org/10.1016/j.cell.2011.07.033] [PMID: 21871655]
[54]
McGettrick, A.F.; O’Neill, L.A.J. The role of HIF in immunity and inflammation. Cell Metab., 2020, 32(4), 524-536.
[http://dx.doi.org/10.1016/j.cmet.2020.08.002] [PMID: 32853548]
[55]
Conradi, L.C.; Brajic, A.; Cantelmo, A.R.; Bouché, A.; Kalucka, J.; Pircher, A.; Brüning, U.; Teuwen, L.A.; Vinckier, S.; Ghesquière, B.; Dewerchin, M.; Carmeliet, P. Tumor vessel disintegration by maximum tolerable PFKFB3 blockade. Angiogenesis, 2017, 20(4), 599-613.
[http://dx.doi.org/10.1007/s10456-017-9573-6] [PMID: 28875379]
[56]
Zhu, W.; Ye, L.; Zhang, J.; Yu, P.; Wang, H.; Ye, Z.; Tian, J. PFK15, a small molecule inhibitor of PFKFB3, induces cell cycle arrest, apoptosis and inhibits invasion in gastric cancer. PLoS One, 2016, 11(9), e0163768.
[http://dx.doi.org/10.1371/journal.pone.0163768] [PMID: 27669567]
[57]
Liu, X.; Zhao, Y.; Zhang, E.; Yan, H.; Lv, N.; Cai, Z. The synergistic effect of PFK15 with metformin exerts anti-myeloma activity via PFKFB3. Biochem. Biophys. Res. Commun., 2019, 515(2), 332-338.
[http://dx.doi.org/10.1016/j.bbrc.2019.05.136] [PMID: 31153642]
[58]
Mondal, S.; Roy, D.; Sarkar Bhattacharya, S.; Jin, L.; Jung, D.; Zhang, S.; Kalogera, E.; Staub, J.; Wang, Y.; Xuyang, W.; Khurana, A.; Chien, J.; Telang, S.; Chesney, J.; Tapolsky, G.; Petras, D.; Shridhar, V. Therapeutic targeting of PFKFB3 with a novel glycolytic inhibitor PFK158 promotes lipophagy and chemosensitivity in gynecologic cancers. Int. J. Cancer, 2019, 144(1), 178-189.
[http://dx.doi.org/10.1002/ijc.31868] [PMID: 30226266]
[59]
Cargill, K.R.; Stewart, C.A.; Park, E.M.; Ramkumar, K.; Gay, C.M.; Cardnell, R.J.; Wang, Q.; Diao, L.; Shen, L.; Fan, Y.H.; Chan, W.K.; Lorenzi, P.L.; Oliver, T.G.; Wang, J.; Byers, L.A. Targeting MYC-enhanced glycolysis for the treatment of small cell lung cancer. Cancer Metab., 2021, 9(1), 33.
[http://dx.doi.org/10.1186/s40170-021-00270-9] [PMID: 34556188]
[60]
Imbert-Fernandez, Y.; Clem, A.; Clem, B.; Tapolsky, G.; Telang, S.; Chesney, J. Abstract 56: Suppression of 6-phosphofructo-2-kinase (PFKFB3) for the treatment of breast cancer. Cancer Res., 2016, (14-Supplement), 56.
[http://dx.doi.org/10.1158/1538-7445.AM2016-56]
[61]
Poels, K.; Schnitzler, J.G.; Waissi, F.; Levels, J.H.M.; Stroes, E.S.G.; Daemen, M.J.A.P.; Lutgens, E.; Pennekamp, A.M.; De Kleijn, D.P.V.; Seijkens, T.T.P.; Kroon, J. Inhibition of PFKFB3 hampers the progression of atherosclerosis and promotes plaque stability. Front. Cell Dev. Biol., 2020, 8, 581641.
[http://dx.doi.org/10.3389/fcell.2020.581641] [PMID: 33282864]
[62]
Chen, L.; Yu, K.; Chen, L.; Zheng, X.; Huang, N.; Lin, Y.; Jia, H.; Liao, W.; Cao, J.; Zhou, T. Synergistic activity of colistin combined with PFK-158 against colistin-resistant and colistin-susceptible Gram-negative bacteria. Research Square, 2020.
[http://dx.doi.org/10.21203/rs.3.rs-86027/v1]
[63]
Telang, S.; Yaddanadupi, K.; Tapolsky, G.; Redman, R.; Chesney, J. Abstract 557: Taking the sweet out of Th17 cells to potentiate immuno-oncology drugs. Cancer Res., 2016, 76(Suppl 14), 557.
[http://dx.doi.org/10.1158/1538-7445.AM2016-557]
[64]
Cantoni, C.; Cignarella, F.; Ghezzi, L.; Mikesell, B.; Bollman, B.; Berrien-Elliott, M.M.; Ireland, A.R.; Fehniger, T.A.; Wu, G.F.; Piccio, L. Mir-223 regulates the number and function of myeloid-derived suppressor cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathol., 2017, 133(1), 61-77.
[http://dx.doi.org/10.1007/s00401-016-1621-6] [PMID: 27704281]

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