Exploring the epigenetic drug discovery landscape

References

• Wu C, Morris JR. Genes, genetics, and epigenetics: a correspondence. Science. 2001;293(5532):1103–1105.
   PubMed Web of Science ®Google Scholar
• Dupont C, Armant DR, Brenner CA. Epigenetics: definition, mechanisms and clinical perspective. Semin Reprod Med. 2009;27(5):351–357.
   PubMed Web of Science ®Google Scholar
• Allfrey V, Faulkner R, Mirsky A. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc Natl Acad Sci USA. 1964;51:786–794.
   PubMed Web of Science ®Google Scholar
• Waddington CH. The epigenotype. 1942. Int J Epidemiol. 2012;41(1):10–13.
   PubMed Web of Science ®Google Scholar
• Noble D. Conrad Waddington and the origin of epigenetics. J Exp Biol. 2015;218(Pt 6):816–818.
   PubMed Web of Science ®Google Scholar
• Gold M, Hurwitz J, Anders M. The enzymatic methylation of RNA and DNA. I. Biochem Biophys Res Commun. 1963;11(2):107–114.
   PubMed Web of Science ®Google Scholar
• Hamm CA, Costa FF. The impact of epigenomics on future drug design and new therapies. Drug Discov Today. 2011;16(13–14):626–635.
   PubMed Web of Science ®Google Scholar
• Gabory A, Attig L, Junien C. Developmental programming and epigenetics. Am J Clin Nutr. 2011;94(6 Suppl):1943S–1952S.
   Google Scholar
• Bhutani N, Burns DM, Blau HM. DNA demethylation dynamics. Cell. 2011;146(6):866–872.
   PubMed Web of Science ®Google Scholar
• Davey CA, Sargent DF, Luger K, et al. Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 Å resolution. J Mol Biol. 2002;319(5):1097–1113.
   PubMed Web of Science ®Google Scholar
• Franchini D-M, Schmitz K-M, Petersen-Mahrt SK. 5-Methylcytosine DNA demethylation: more than losing a methyl group. Annu Rev Genet. 2012;46:419–441.
   PubMed Web of Science ®Google Scholar
• Messerschmidt DM, Knowles BB, Solter D. DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev. 2014;28(8):812–828.
   PubMed Web of Science ®Google Scholar
• Mariño-Ramírez L, Kann MG, Shoemaker BA, et al. Histone structure and nucleosome stability. Expert Rev Proteomics. 2005;2(5):719–729.
   PubMed Web of Science ®Google Scholar
• Meng F, Wang C, Wan W, et al. Discovery and development of small molecules targeting epigenetic enzymes with computational methods. In: Medina-Franco JL, Ed. Epi-Informatics: discovery and development of small molecule epigenetic drugs and probes. London: Elsevier Inc; 2016. p. 75–112.
   Google Scholar
• Falkenberg KJ, Johnstone RW. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov. 2014;13(9):673–691.
   PubMed Web of Science ®Google Scholar
• Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21(3):381–395.
   PubMed Web of Science ®Google Scholar
• Fu X-D. Non-coding RNA: a new frontier in regulatory biology. Natl Sci Rev. 2014;1(2):190–204.
   PubMed Web of Science ®Google Scholar
• Mirbahai L, Chipman JK. Epigenetic memory of environmental organisms: a reflection of lifetime stressor exposures. Mutat Res Genet Toxicol Environ Mutagen. 2014;764-765:10–17.
   PubMed Web of Science ®Google Scholar
• Patkin EL, Sofronov GA. Population epigenetics, ecotoxicology, and human diseases. Russ J Genet Appl Res. 2013;3(5):338–351.
   Google Scholar
• Prins GS, Birch L, Tang W-Y, et al. Developmental estrogen exposures predispose to prostate carcinogenesis with aging. Reprod Toxicol. 2007;23(3):374–382.
   PubMed Web of Science ®Google Scholar
• Cazaly E, Charlesworth J, Dickinson JL, et al. Genetic determinants of epigenetic patterns: providing insight into disease. Mol Med. 2015;21:400–409.
   PubMed Web of Science ®Google Scholar
• Gaulton A, Hersey A, Nowotka M, et al. The ChEMBL database in 2017. Nucleic Acids Res. 2017;45(D1):D945–D954.
   PubMed Web of Science ®Google Scholar
• Singh Nanda J, Kumar R, Raghava GPS. dbEM: a database of epigenetic modifiers curated from cancerous and normal genomes. Sci Rep. 2016;6:19340.
   PubMed Web of Science ®Google Scholar
• Huang Z, Jiang H, Liu X, et al. HEMD: an integrated tool of human epigenetic enzymes and chemical modulators for therapeutics. Plos ONE. 2012;7(6):e39917.
   PubMed Web of Science ®Google Scholar
• Nantasenamat C, Prachayasittikul V. Maximizing computational tools for successful drug discovery. Expert Opin Drug Discov. 2015;10(4):321–329.
   PubMed Web of Science ®Google Scholar
• Lapinsh M, Prusis P, Gutcaits A, et al. Development of proteo-chemometrics: a novel technology for the analysis of drug-receptor interactions. Biochim Biophys Acta. 2001;1525(1–2):180–190.
   PubMed Web of Science ®Google Scholar
• Cortés-Ciriano I, Ain QU, Subramanian V, et al. Polypharmacology modelling using proteochemometrics (PCM): recent methodological developments, applications to target families, and future prospects. Med Chem Commun. 2015;6(1):24–50.
   Web of Science ®Google Scholar
• Robertson KD. DNA methylation, methyltransferases, and cancer. Oncogene. 2001;20(24):3139–3155.
   PubMed Web of Science ®Google Scholar
• Cheng X, Roberts RJ. AdoMet-dependent methylation, DNA methyltransferases and base flipping. Nucleic Acids Res. 2001;29(18):3784–3795.
   PubMed Web of Science ®Google Scholar
• Fellinger K, Rothbauer U, Felle M, et al. Dimerization of DNA methyltransferase 1 is mediated by its regulatory domain. J Cell Biochem. 2009;106(4):521–528.
   PubMed Web of Science ®Google Scholar
• Rai K, Chidester S, Zavala CV, et al. Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish. Genes Dev. 2007;21(3):261–266.
   PubMed Web of Science ®Google Scholar
• Schaefer M, Pollex T, Hanna K, et al. RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes Dev. 2010;24(15):1590–1595.
   PubMed Web of Science ®Google Scholar
• Jia D, Jurkowska RZ, Zhang X, et al. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature. 2007;449(7159):248–251.
   PubMed Web of Science ®Google Scholar
• Guianvarc’h D, Arimondo PB. Challenges in developing novel DNA methyltransferase inhibitors for cancer therapy. Future Medicinal Chemistry. 2014;6(11):1237–1240.
   PubMed Web of Science ®Google Scholar
• Copeland RA, Olhava EJ, Scott MP. Targeting epigenetic enzymes for drug discovery. Curr Opin Chem Biol. 2010;14(4):505–510.
   PubMed Web of Science ®Google Scholar
• Erdmann A, Halby L, Fahy J, et al. Targeting DNA methylation with small molecules: what’s next? J Med Chem. 2015;58(6):2569–2583.
   PubMed Web of Science ®Google Scholar
• Gaulton A, Bellis LJ, Bento AP, et al. ChEMBL: a large-scale bioactivity database for drug discovery. Nucleic Acids Res. 2012;40(Database issue):D1100–7.
   PubMed Web of Science ®Google Scholar
• Yoo CB, Jeong S, Egger G, et al. Delivery of 5-aza-2ʹ-deoxycytidine to cells using oligodeoxynucleotides. Cancer Res. 2007;67(13):6400–6408.
   PubMed Web of Science ®Google Scholar
• Griffiths EA, Choy G, Redkar S, et al. SGI-110: DNA methyltransferase inhibitor oncolytic. Drugs Future. 2013;38(8):535–543.
   PubMed Web of Science ®Google Scholar
• Cohen I, Poręba E, Kamieniarz K, et al. Histone modifiers in cancer: friends or foes? Genes Cancer. 2011;2(6):631–647.
   PubMedGoogle Scholar
• Rodríguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat Med. 2011;17(3):330–339.
   PubMed Web of Science ®Google Scholar
• Balasubramanyam K, Varier RA, Altaf M, et al. Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem. 2004;279(49):51163–51171.
   PubMed Web of Science ®Google Scholar
• Mukhopadhyay A, Banerjee S, Stafford LJ, et al. Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation. Oncogene. 2002;21(57):8852–8861.
   PubMed Web of Science ®Google Scholar
• Delcuve GP, Khan DH, Davie JR. Roles of histone deacetylases in epigenetic regulation: emerging paradigms from studies with inhibitors. Clin Epigenetics. 2012;4(1):5.
   PubMed Web of Science ®Google Scholar
• Thangapandian S, John S, Sakkiah S, et al. Ligand and structure based pharmacophore modeling to facilitate novel histone deacetylase 8 inhibitor design. Eur J Med Chem. 2010;45(10):4409–4417.
   PubMed Web of Science ®Google Scholar
• Ononye SN, Van Heyst M, Falcone EM, et al. Toward isozyme-selective inhibitors of histone deacetylase as therapeutic agents for the treatment of cancer. Pharm Pat Anal. 2012;1(2):207–221.
   PubMedGoogle Scholar
• Nebbioso A, Carafa V, Benedetti R, et al. Trials with “epigenetic” drugs: an update. Mol Oncol. 2012;6(6):657–682.
   PubMed Web of Science ®Google Scholar
• West AC, Johnstone RW. New and emerging HDAC inhibitors for cancer treatment. J Clin Invest. 2014;124(1):30–39.
   PubMed Web of Science ®Google Scholar
• Mottamal M, Zheng S, Huang TL, et al. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules. 2015;20(3):3898–3941.
   PubMed Web of Science ®Google Scholar
• Wang D. Computational studies on the histone deacetylases and the design of selective histone deacetylase inhibitors. Curr Top Med Chem. 2009;9(3):241–256.
   PubMed Web of Science ®Google Scholar
• Bradner JE, West N, Grachan ML, et al. Chemical phylogenetics of histone deacetylases. Nat Chem Biol. 2010;6(3):238–243.
   PubMed Web of Science ®Google Scholar
• Chen K, Xu L, Wiest O. Computational exploration of zinc binding groups for HDAC inhibition. J Org Chem. 2013;78(10):5051–5055.
   PubMed Web of Science ®Google Scholar
• Mahajan SS, Leko V, Simon JA, et al. Sirtuin modulators. Handb Exp Pharmacol. 2011;206:241–255.
   PubMedGoogle Scholar
• Walport LJ, Hopkinson RJ, Chowdhury R, et al. Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases. Nat Commun. 2016;7:11974.
   PubMed Web of Science ®Google Scholar
• https://www.ncbi.nlm.nih.gov/pubmed/15971202
   Google Scholar
• Kim YZ. Protein methylation and demethylation in cancer. Int J Neurol Res. 2015;1(3):129–140.
   Google Scholar
• Thinnes CC, England KS, Kawamura A, et al. Targeting histone lysine demethylases - progress, challenges, and the future. Biochim Biophys Acta. 2014;1839(12):1416–1432.
   PubMed Web of Science ®Google Scholar
• Copeland RA, Moyer MP, Richon VM. Targeting genetic alterations in protein methyltransferases for personalized cancer therapeutics. Oncogene. 2013;32(8):939–946.
   PubMed Web of Science ®Google Scholar
• Boriack-Sjodin PA, Swinger KK. Protein methyltransferases: a distinct, diverse, and dynamic family of enzymes. Biochemistry. 2016;55(11):1557–1569.
   PubMed Web of Science ®Google Scholar
• Schapira M, Arrowsmith CH. Methyltransferase inhibitors for modulation of the epigenome and beyond. Curr Opin Chem Biol. 2016;33:81–87.
   PubMed Web of Science ®Google Scholar
• Simó-Riudalbas L, Esteller M. Targeting the histone orthography of cancer: drugs for writers, erasers and readers. Br J Pharmacol. 2015;172(11):2716–2732.
   PubMed Web of Science ®Google Scholar
• Gelato KA, Shaikhibrahim Z, Ocker M, et al. Targeting epigenetic regulators for cancer therapy: modulation of bromodomain proteins, methyltransferases, demethylases, and microRNAs. Expert Opin Ther Targets. 2016;20(7):783–799.
   PubMed Web of Science ®Google Scholar
• Copeland RA. Protein methyltransferase inhibitors as personalized cancer therapeutics. Drug Discov Today: Ther Strateg. 2012;9(2–3):e83–e90.
   Google Scholar
• Spannhoff A, Machmur R, Heinke R, et al. A novel arginine methyltransferase inhibitor with cellular activity. Bioorg Med Chem Lett. 2007;17(15):4150–4153.
   PubMed Web of Science ®Google Scholar
• Selvi BR, Batta K, Kishore AH, et al. Identification of a novel inhibitor of coactivator-associated arginine methyltransferase 1 (CARM1)-mediated methylation of histone H3 Arg-17. J Biol Chem. 2010;285(10):7143–7152.
   PubMed Web of Science ®Google Scholar
• Chan-Penebre E, Kuplast KG, Majer CR, et al. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nat Chem Biol. 2015;11(6):432–437.
   PubMed Web of Science ®Google Scholar
• Cheng D, Yadav N, King RW, et al. Small molecule regulators of protein arginine methyltransferases. J Biol Chem. 2004;279(23):23892–23899.
   PubMed Web of Science ®Google Scholar
• El Messaoudi S, Fabbrizio E, Rodriguez C, et al. Coactivator-associated arginine methyltransferase 1 (CARM1) is a positive regulator of the Cyclin E1 gene. Proc Natl Acad Sci USA. 2006;103(36):13351–13356.
   PubMed Web of Science ®Google Scholar
• Mai A, Cheng D, Bedford MT, et al. Epigenetic multiple ligands: mixed histone/protein methyltransferase, acetyltransferase, and class III deacetylase (sirtuin) inhibitors. J Med Chem. 2008;51(7):2279–2290.
   PubMed Web of Science ®Google Scholar
• Galdeano C, Ciulli A. Selectivity on-target of bromodomain chemical probes by structure-guided medicinal chemistry and chemical biology. Future Med Chem. 2016;8(13):1655–1680.
   PubMed Web of Science ®Google Scholar
• Nicholls SJ, Puri R, Wolski K, et al. Effect of the BET protein inhibitor, RVX-208, on progression of coronary atherosclerosis: results of the phase 2b, randomized, double-blind, multicenter, ASSURE trial. Am J Cardiovasc Drugs. 2016;16(1):55–65.
   PubMed Web of Science ®Google Scholar
• Shu S, Polyak K. BET bromodomain proteins as cancer therapeutic targets. Cold Spring Harb Symp Quant Biol. 2017;81. doi:10.1101/sqb.2016.81.030908.
   PubMedGoogle Scholar
• Romero FA, Taylor AM, Crawford TD, et al. Disrupting acetyl-lysine recognition: progress in the development of bromodomain inhibitors. J Med Chem. 2016;59(4):1271–1298.
   PubMed Web of Science ®Google Scholar
• Albrecht BK, Gehling VS, Hewitt MC, et al. Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) family as a candidate for human clinical trials. J Med Chem. 2016;59(4):1330–1339.
   PubMed Web of Science ®Google Scholar
• Bieliauskas AV, Pflum MKH. Isoform-selective histone deacetylase inhibitors. Chem Soc Rev. 2008;37(7):1402–1413.
   PubMed Web of Science ®Google Scholar
• Tak YG, Farnham PJ. Making sense of GWAS: using epigenomics and genome engineering to understand the functional relevance of SNPs in non-coding regions of the human genome. Epigenetics Chromatin. 2015;8:57.
   PubMed Web of Science ®Google Scholar
• Wu C, Jin X, Tsueng G, et al. BioGPS: building your own mash-up of gene annotations and expression profiles. Nucleic Acids Res. 2016;44(D1):D313–6.
   PubMed Web of Science ®Google Scholar
• Reilly CM, Regna N, Mishra N. HDAC inhibition in lupus models. Mol Med. 2011;17(5–6):417–425.
   PubMed Web of Science ®Google Scholar
• Pandian GN, Taniguchi J, Junetha S, et al. Distinct DNA-based epigenetic switches trigger transcriptional activation of silent genes in human dermal fibroblasts. Sci Rep. 2014;4:3843.
   PubMed Web of Science ®Google Scholar
• Katsila T, Spyroulias GA, Patrinos GP, et al. Computational approaches in target identification and drug discovery. Comput Struct Biotechnol J. 2016;14:177–184.
   PubMed Web of Science ®Google Scholar
• Lussier YA, Chen JL. The emergence of genome-based drug repositioning. Sci Transl Med. 2011;3(96):96ps35.
   PubMed Web of Science ®Google Scholar
• Iwata H, Sawada R, Mizutani S, et al. Systematic drug repositioning for a wide range of diseases with integrative analyses of phenotypic and molecular data. J Chem Inf Model. 2015;55(2):446–459.
   PubMed Web of Science ®Google Scholar
• Prathipati P, Mizuguchi K. Systems biology approaches to a rational drug discovery paradigm. Curr Top Med Chem. 2016;16(9):1009–1025.
   PubMed Web of Science ®Google Scholar
• Naveja JJ, Dueñas-González A, Medina-Franco JL. Drug repurposing for epigenetic targets guided by computational methods. In: Medina-Franco JL, Ed.. Epi-Informatics. London, UK: Elsevier Inc; 2016. p. 327–357.
   Google Scholar
• Méndez-Lucio O, Tran J, Medina-Franco JL, et al. Toward drug repurposing in epigenetics: olsalazine as a hypomethylating compound active in a cellular context. ChemMedChem. 2014;9(3):560–565.
   PubMed Web of Science ®Google Scholar
• De La Cruz-Hernandez E, Medina-Franco JL, Trujillo J, et al. Ribavirin as a tri-targeted antitumor repositioned drug. Oncol Rep. 2015;33(5):2384–2392.
   PubMed Web of Science ®Google Scholar
• Dakshanamurthy S, Issa NT, Assefnia S, et al. Predicting new indications for approved drugs using a proteochemometric method. J Med Chem. 2012;55(15):6832–6848.
   PubMed Web of Science ®Google Scholar
• Claerhout S, Lim JY, Choi W, et al. Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer. PLos ONE. 2011;6(9):e24662.
   PubMed Web of Science ®Google Scholar
• Wen Z, Wang Z, Wang S, et al. Discovery of molecular mechanisms of traditional Chinese medicinal formula Si-Wu-Tang using gene expression microarray and connectivity map. Plos ONE. 2011;6(3):e18278.
   Google Scholar
• Lamb J, Crawford ED, Peck D, et al. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006;313(5795):1929–1935.
   PubMed Web of Science ®Google Scholar
• Zerbini LF, Bhasin MK, De Vasconcellos JF, et al. Computational repositioning and preclinical validation of pentamidine for renal cell cancer. Mol Cancer Ther. 2014;13(7):1929–1941.
   PubMed Web of Science ®Google Scholar
• Oprea TI, Overington JP. Computational and practical aspects of drug repositioning. Assay Drug Dev Technol. 2015;13(6):299–306.
   PubMed Web of Science ®Google Scholar
• Wishart DS, Knox C, Guo AC, et al. DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2006;34(Database issue):D668–672.
   PubMed Web of Science ®Google Scholar
• Edgar R, Domrachev M, Lash AE. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002;30(1):207–10.
   PubMed Web of Science ®Google Scholar
• Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.
   PubMed Web of Science ®Google Scholar
• Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007;128(4):683–692.
   PubMed Web of Science ®Google Scholar
• Mencher SK, Wang LG. Promiscuous drugs compared to selective drugs (promiscuity can be a virtue). BMC Clin Pharmacol. 2005;5:3.
   PubMedGoogle Scholar