Phosphoglycerate dehydrogenase (PHGDH) inhibitors: a comprehensive review 2015–2020

References

• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674.
   PubMed Web of Science ®Google Scholar
• Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab. 2016;23:27–47.
   PubMed Web of Science ®Google Scholar
• Phan LM, Yeung SCJ, Lee MH. Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies. Cancer Biol Med. 2014;11:1–19.
   PubMedGoogle Scholar
• Warburg. On the origin of cancer cells. Science . 1956;123: 309–314. (80-.).
   PubMed Web of Science ®Google Scholar
• Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science . 2009;324: 1029–1033. (80-.).
   PubMed Web of Science ®Google Scholar
• Mattaini KR, Sullivan MR, Vander Heiden MG. The importance of serine metabolism in cancer. J Cell Biol. 2016;214:249–257.
   PubMed Web of Science ®Google Scholar
• Snell K, Natsumeda Y, Weber G. The modulation of serine metabolism in hepatoma 3924A during different phases of cellular proliferation in culture. Biochem J. 1987;245:609–612.
   PubMed Web of Science ®Google Scholar
• Pollari S, Käkönen S, Edgren H, et al. Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis. Breast Cancer Res Treat. 2011;125:421–430.
   PubMed Web of Science ®Google Scholar
• Locasale JW, Grassian AR, Melman T, et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat Genet. 2011;43:869–874.
   PubMed Web of Science ®Google Scholar
• Possemato R, Marks KM, Shaul YD, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011;476:346–350.
   PubMed Web of Science ®Google Scholar
• Locasale JW. Serine, Glycine and the one-carbon cycle: cancer metabolism in full circle. Nat Rev Cancer. 2013;13:572–583.
   PubMed Web of Science ®Google Scholar
• Luo J. Cancer’s sweet tooth for serine. Breast Cancer Res. 2011;13:317.
   PubMed Web of Science ®Google Scholar
• Pacold ME, Brimacombe KR, Chan SH, et al. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat Chem Biol. 2016;12:452–458.
   PubMed Web of Science ®Google Scholar
• Zhang B, Zheng A, Hydbring P, et al. PHGDH defines a metabolic subtype in lung adenocarcinomas with poor prognosis. Cell Rep. 2017;19:2289–2303.
   PubMed Web of Science ®Google Scholar
• Samanta D, Park Y, Andrabi SA, et al. PHGDH expression is required for mitochondrial redox homeostasis, breast cancer stem cell maintenance, and lung metastasis. Cancer Res. 2016;76:4430–4442.
   PubMed Web of Science ®Google Scholar
• Shiota M, Naya M, Yamamoto T, et al. Gold-nanofiber surface-enhanced Raman spectroscopy visualizes hypotaurine as a robust anti-oxidant consumed in cancer survival. Nat Commun. 2018;9:1561.
   PubMed Web of Science ®Google Scholar
• Liu J, Guo S, Li Q, et al. Phosphoglycerate dehydrogenase induces glioma cells proliferation and invasion by stabilizing forkhead box M1. J Neurooncol. 2013;111:245–255.
   PubMed Web of Science ®Google Scholar
• Wierstra I. FOXM1 (forkhead box M1) in tumorigenesis: overexpression in human cancer, implication in tumorigenesis, oncogenic functions, tumor-suppressive properties, and target of anticancer therapy. In Advances in cancer research. San Diego (CA): Elsevier Academic Press; 2013;191–419.
   Google Scholar
• Fan J, Teng X, Liu L, et al. Human phosphoglycerate dehydrogenase produces the oncometabolite d-2-Hydroxyglutarate. ACS Chem Biol. 2015;10:510–516.
   PubMed Web of Science ®Google Scholar
• Song Z, Feng C, Lu Y, et al. PHGDH is an independent prognosis marker and contributes cell proliferation, migration and invasion in human pancreatic cancer. Gene. 2018;642:43–50.
   PubMed Web of Science ®Google Scholar
• Sun WY, Kim HM, Jung WH, et al. Expression of serine/glycine metabolism-related proteins is different according to the thyroid cancer subtype. J Transl Med. 2016;14:168.
   PubMed Web of Science ®Google Scholar
• Amelio I, Markert EK, Antonov AV, et al. P73 regulates serine biosynthesis in cancer. Oncogene. 2014;33:5039–5046.
   PubMed Web of Science ®Google Scholar
• Mullarky E, Mattaini KR, Vander Heiden MG, et al. PHGDH amplification and altered glucose metabolism in human melanoma. Pigment Cell Melanoma Res. 2011;24:1112–1115.
   PubMed Web of Science ®Google Scholar
• Proteopedia: HI. Rossmann fold: a beta-alpha-beta fold at dinucleotide-binding sites. Biochem Mol Biol Educ. 2015;43:206–209.
   PubMed Web of Science ®Google Scholar
• Fuller N, Spadola L, Cowen S, et al. An improved model for fragment-based lead generation at AstraZeneca. Drug Discov Today. 2016;21:1272–1283.
   PubMed Web of Science ®Google Scholar
• Mullarky E, Xu J, Robin AD, et al. Inhibition of 3-phosphoglycerate dehydrogenase (PHGDH) by indole amides abrogates de novo serine synthesis in cancer cells. Bioorg Med Chem Lett. 2019;29:2503–2510.
   PubMed Web of Science ®Google Scholar
• Weinstabl H, Treu M, Rinnenthal J, et al. Intracellular Trapping of the Selective Phosphoglycerate Dehydrogenase (PHGDH) Inhibitor BI-4924 Disrupts Serine Biosynthesis. J Med Chem. 2019;62:7976–7997.
   PubMed Web of Science ®Google Scholar
• Mullarky E, Lucki NC, Zavareh RB, et al. Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers. Proc Natl Acad Sci. 2016;113:201521548.
   Web of Science ®Google Scholar
• Raze Therapeutics Inc. Indole-2-carboxamides as 3-phosphoglycerate dehydrogenase inhibitors and their preparation. WO2017156181A1. 2017.
   Google Scholar
• Raze Therapeutics Inc. Indole-2-carboxamides as 3-phosphoglycerate dehydrogenase inhibitors and their preparation. WO2017156165A1. 2017.
   Google Scholar
• Raze Therapeutics Inc. Indole-2-carboxamides as 3-phosphoglycerate dehydrogenase inhibitors and their preparation. WO2017156177A1. 2017.
   Google Scholar
• Mullarky E, Lairson LL, Cantley LC, et al. A novel small-molecule inhibitor of 3-phosphoglycerate dehydrogenase. Mol Cell Oncol. 2016;3:e1164280.
   PubMed Web of Science ®Google Scholar
• Spillier Q, Vertommen D, Ravez S, et al. Anti-alcohol abuse drug disulfiram inhibits human PHGDH via disruption of its active tetrameric form through a specific cysteine oxidation. Sci Rep. 2019;9:4737.
   PubMed Web of Science ®Google Scholar
• Cantley LC, Mullarky E, Lyssiotis C, et al. Preparation of small molecule inhibitors of 3-phosphoglycerate dehydrogenase (PHGDH). WO2017117532A1. 2017.
   Google Scholar
• Beth Israel Deaconess Medical Center Inc. Methods and compositions for the diagnosis and treatment of cellular proliferative disorders. US20130203618A1. 2013.
   Google Scholar
• Rohde JM, Brimacombe KR, Liu L, et al. Discovery and optimization of piperazine-1-thiourea-based human phosphoglycerate dehydrogenase inhibitors. Bioorg Med Chem. 2018;26:1727–1739.
   PubMed Web of Science ®Google Scholar
• Whitehead Institute for Biomedical Research, Dana-Farber Cancer Institute Inc. Inhibitors of phosphoglycerate dehydrogenase (PHGDH) and uses thereof. WO2016115463A1. 2016.
   Google Scholar
• RavezS, Corbet C, Spillier Q, et al. α-ketothioamide derivatives: a promising tool to interrogate phosphoglycerate dehydrogenase (PHGDH). J Med Chem. 2017;60:1591–1597.
   PubMed Web of Science ®Google Scholar
• Spillier Q, Ravez S, Unterlass J, et al. Structure–activity relationships (sars) of α-ketothioamides as inhibitors of phosphoglycerate dehydrogenase (PHGDH). Pharmaceuticals. 2020;13:20.
   Web of Science ®Google Scholar
• Ravez S, Corbet C, Spillier Q, et al. Preparation of substituted carbothioamide compounds as serine biosynthetic pathway inhibitors for treatment of cancer, WO 2017157882. (2017).
   Google Scholar
• Spillier Q, RavezS,Dochain S, et al. Unravelling the allosteric targeting of PHGDH at the end mass spectrometry experiments. Molecules. 2021;26:477.
   PubMed Web of Science ®Google Scholar
• Njoroge FG, Chen KX, Shih N-Y, et al. Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection. Acc Chem Res. 2008;41:50–59.
   PubMed Web of Science ®Google Scholar
• Raze Therapeutics Inc. 3-Phosphoglycerate dehydrogenase inhibitors and uses thereof. WO. 2016;2016/040449.
   Google Scholar
• Wang Q, et al. Rational design of selective allosteric inhibitors of PHGDH and serine synthesis with anti-tumor activity. Cell Chem Biol. 2016;24:55–65.
   PubMed Web of Science ®Google Scholar
• Peking University. D-3-phosphoglycerate dehydrogenase allosteric inhibitor and use thereof. WO2018076537A1. 2018.
   Google Scholar
• Peking University. Benzoyl hydrazine D-3-phosphoglycerate dehydrogenase allosteric inhibitor and use thereof. CN106562946A. 2017.
   Google Scholar
• Guo J, et al. Azacoccone E inhibits cancer cell growth by targeting 3-phosphoglycerate dehydrogenase. Bioorg Chem. 2019;87:16–22.
   PubMed Web of Science ®Google Scholar
• Zheng M, et al. Ixocarpalactone A from dietary tomatillo inhibits pancreatic cancer growth by targeting PHGDH. Food Funct. 2019;10:3386–3395.
   PubMed Web of Science ®Google Scholar
• Spillier, et al. Structure–activity relationships (sars) of α-ketothioamides as inhibitors of phosphoglycerate dehydrogenase (PHGDH). Pharmaceuticals. 2020;13:20.
   Web of Science ®Google Scholar
• Raze Therapeutics Inc. 3-Phosphoglycerate dehydrogenase inhibitors and uses thereof. WO2016040449A1. 2016.
   Google Scholar
• Ngo B, et al. Limited environmental serine and glycine confer brain metastasis sensitivity to PHGDH inhibition. Cancer Discov. 2020;10:1352–1373.
   PubMed Web of Science ®Google Scholar
• Yan Z, Zhou Z, Wu Q, et al. Presymptomatic Increase of an extracellular RNA in blood plasma associates with the development of alzheimer’s disease. Curr Biol. 2020;30(1771–1782.e3).
   Google Scholar
• Bruegger JJ, Smith BC, Wynia-Smith SL, et al. Comparative and integrative metabolomics reveal that S-nitrosation inhibits physiologically relevant metabolic enzymes. J Biol Chem. 2018;293:6282–6296.
   PubMed Web of Science ®Google Scholar
• Nigdelioglu R, et al. Transforming growth factor (TGF)-β promotes de novo serine synthesis for collagen production. J Biol Chem. 2016;291:27239–27251.
   PubMed Web of Science ®Google Scholar
• Unterlass JE, et al. Structural insights into the enzymatic activity and potential substrate promiscuity of human 3-phosphoglycerate dehydrogenase (PHGDH). Oncotarget. 2017;8:104478–104491.
   PubMedGoogle Scholar
• Zaal EA, et al. Bortezomib resistance in multiple myeloma is associated with increased serine synthesis. Cancer Metab. 2017;5:7.
   PubMed Web of Science ®Google Scholar
• Zhang X, Bai W. Repression of phosphoglycerate dehydrogenase sensitizes triple-negative breast cancer to doxorubicin. Cancer Chemother Pharmacol. 2016;78:655–659.
   PubMed Web of Science ®Google Scholar
• Ross KC, Andrews AJ, Marion CD, et al. Identification of the serine biosynthesis pathway as a critical component of braf inhibitor resistance of melanoma, pancreatic, and non–small cell lung cancer cells. Mol Cancer Ther. 2017;16:1596–1609.
   PubMed Web of Science ®Google Scholar
• Dong JK, et al. Overcoming erlotinib resistance in EGFR mutation-positive lung adenocarcinomas through repression of phosphoglycerate dehydrogenase. Theranostics. 2018;8:1808–1823.
   PubMed Web of Science ®Google Scholar