Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Protein Lysine Methyltransferases Inhibitors

Author(s): Ying Li, Lei Ding, Shuang Ren, Wen Zhang and Guo-Wu Rao*

Volume 30, Issue 27, 2023

Published on: 14 November, 2022

Page: [3060 - 3089] Pages: 30

DOI: 10.2174/0929867329666220829151257

Price: $65

Abstract

Protein lysine methylation is a significant protein post-translational modification (PTMs) and has a key function in epigenetic regulation. Protein lysine methyltransferase (PKMTs) mainly catalyzes the lysine methylation of various core histones and a few non-histone proteins. It has been observed that aberrant activity of PKMTs has been found in many cancers and other diseases, and some PKMT inhibitors have been discovered and progressed to clinical trials. This field developed rapidly and has aroused great interest. In this paper, we reviewed the biochemical and biological activities of PKMTs and their association with various cancers. Selective small-molecule inhibitors, including their chemical structure, structure-activity relationship, and in vitro/vivo studies, are also described to provide ideas for the discovery of highly potent, selective PKMT inhibitors.

Keywords: Epigenetics, methylation, protein lysine, methyltransferases, cancer, small molecular, inhibitors.

[1]
Allis, C.D.; Jenuwein, T. The molecular hallmarks of epigenetic control. Nat. Rev. Genet., 2016, 17(8), 487-500.
[http://dx.doi.org/10.1038/nrg.2016.59] [PMID: 27346641]
[2]
Berger, S.L.; Kouzarides, T.; Shiekhattar, R.; Shilatifard, A. An operational definition of epigenetics. Genes Dev., 2009, 23(7), 781-783.
[http://dx.doi.org/10.1101/gad.1787609] [PMID: 19339683]
[3]
Jones, P.A.; Baylin, S.B. The epigenomics of cancer. Cell, 2007, 128(4), 683-692.
[http://dx.doi.org/10.1016/j.cell.2007.01.029] [PMID: 17320506]
[4]
Bernstein, B.E.; Meissner, A.; Lander, E.S. The mammalian epigenome. Cell, 2007, 128(4), 669-681.
[http://dx.doi.org/10.1016/j.cell.2007.01.033] [PMID: 17320505]
[5]
Wu, C.; Morris, J.R. Genes, genetics, and epigenetics: A correspondence. Science, 2001, 293(5532), 1103-1105.
[http://dx.doi.org/10.1126/science.293.5532.1103] [PMID: 11498582]
[6]
Bird, A. Perceptions of epigenetics. Nature, 2007, 447(7143), 396-398.
[http://dx.doi.org/10.1038/nature05913] [PMID: 17522671]
[7]
Lee, J.S.; Smith, E.; Shilatifard, A. The language of histone crosstalk. Cell, 2010, 142(5), 682-685.
[http://dx.doi.org/10.1016/j.cell.2010.08.011] [PMID: 20813257]
[8]
Luger, K.; Mäder, A.W.; Richmond, R.K.; Sargent, D.F.; Richmond, T.J. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature, 1997, 389(6648), 251-260.
[http://dx.doi.org/10.1038/38444] [PMID: 9305837]
[9]
Khorasanizadeh, S. The Nucleosome. Cell, 2004, 116(2), 259-272.
[http://dx.doi.org/10.1016/S0092-8674(04)00044-3] [PMID: 14744436]
[10]
Dixon, J.R.; Selvaraj, S.; Yue, F.; Kim, A.; Li, Y.; Shen, Y.; Hu, M.; Liu, J.S.; Ren, B. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature, 2012, 485(7398), 376-380.
[http://dx.doi.org/10.1038/nature11082] [PMID: 22495300]
[11]
Kouzarides, T. Chromatin modifications and their function. Cell, 2007, 128(4), 693-705.
[http://dx.doi.org/10.1016/j.cell.2007.02.005] [PMID: 17320507]
[12]
Strahl, B.D.; Allis, C.D. The language of covalent histone modifications. Nature, 2000, 403(6765), 41-45.
[http://dx.doi.org/10.1038/47412] [PMID: 10638745]
[13]
Teif, V.B.; Bohinc, K.; Condensed, D.N.A. Condensed DNA: Condensing the concepts. Prog. Biophys. Mol. Biol., 2011, 105(3), 208-222.
[http://dx.doi.org/10.1016/j.pbiomolbio.2010.07.002] [PMID: 20638406]
[14]
Gelato, K.A.; Fischle, W. Role of histone modifications in defining chromatin structure and function. Biol. Chem., 2008, 389(4), 353-363.
[http://dx.doi.org/10.1515/BC.2008.048] [PMID: 18225984]
[15]
Verdone, L.; Agricola, E.; Caserta, M.; Di Mauro, E. Histone acetylation in gene regulation. Brief. Funct. Genomics Proteomics, 2006, 5(3), 209-221.
[http://dx.doi.org/10.1093/bfgp/ell028] [PMID: 16877467]
[16]
Kristeleit, R.; Stimson, L.; Workman, P.; Aherne, W. Histone modification enzymes: Novel targets for cancer drugs. Expert Opin. Emerg. Drugs, 2004, 9(1), 135-154.
[http://dx.doi.org/10.1517/14728214.9.1.135] [PMID: 15155140]
[17]
Rea, S.; Eisenhaber, F.; O’Carroll, D.; Strahl, B.D.; Sun, Z.W.; Schmid, M.; Opravil, S.; Mechtler, K.; Ponting, C.P.; Allis, C.D.; Jenuwein, T. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature, 2000, 406(6796), 593-599.
[http://dx.doi.org/10.1038/35020506] [PMID: 10949293]
[18]
Kaniskan, H.Ü.; Konze, K.D.; Jin, J. Selective inhibitors of protein methyltransferases. J. Med. Chem., 2015, 58(4), 1596-1629.
[http://dx.doi.org/10.1021/jm501234a] [PMID: 25406853]
[19]
Copeland, R.A.; Solomon, M.E.; Richon, V.M. Protein methyltransferases as a target class for drug discovery. Nat. Rev. Drug Discov., 2009, 8(9), 724-732.
[http://dx.doi.org/10.1038/nrd2974] [PMID: 19721445]
[20]
Shi, Y.; Lan, F.; Matson, C.; Mulligan, P.; Whetstine, J.R.; Cole, P.A.; Casero, R.A.; Shi, Y. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell, 2004, 119(7), 941-953.
[http://dx.doi.org/10.1016/j.cell.2004.12.012] [PMID: 15620353]
[21]
Karytinos, A.; Forneris, F.; Profumo, A.; Ciossani, G.; Battaglioli, E.; Binda, C.; Mattevi, A. A novel mammalian flavin-dependent histone demethylase. J. Biol. Chem., 2009, 284(26), 17775-17782.
[http://dx.doi.org/10.1074/jbc.M109.003087] [PMID: 19407342]
[22]
Shi, X.; Kachirskaia, I.; Yamaguchi, H.; West, L.E.; Wen, H.; Wang, E.W.; Dutta, S.; Appella, E.; Gozani, O. Modulation of p53 function by SET8-mediated methylation at lysine 382. Mol. Cell, 2007, 27(4), 636-646.
[http://dx.doi.org/10.1016/j.molcel.2007.07.012] [PMID: 17707234]
[23]
Chuikov, S.; Kurash, J.K.; Wilson, J.R.; Xiao, B.; Justin, N.; Ivanov, G.S.; McKinney, K.; Tempst, P.; Prives, C.; Gamblin, S.J.; Barlev, N.A.; Reinberg, D. Regulation of p53 activity through lysine methylation. Nature, 2004, 432(7015), 353-360.
[http://dx.doi.org/10.1038/nature03117] [PMID: 15525938]
[24]
Autiero, M.; Luttun, A.; Tjwa, M.; Carmeliet, P. Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: Novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders. J. Thromb. Haemost., 2003, 1(7), 1356-1370.
[http://dx.doi.org/10.1046/j.1538-7836.2003.00263.x] [PMID: 12871269]
[25]
Huang, J.; Perez-Burgos, L.; Placek, B.J.; Sengupta, R.; Richter, M.; Dorsey, J.A.; Kubicek, S.; Opravil, S.; Jenuwein, T.; Berger, S.L. Repression of p53 activity by Smyd2-mediated methylation. Nature, 2006, 444(7119), 629-632.
[http://dx.doi.org/10.1038/nature05287] [PMID: 17108971]
[26]
Saddic, L.A.; West, L.E.; Aslanian, A.; Yates, J.R., III; Rubin, S.M.; Gozani, O.; Sage, J. Methylation of the retinoblastoma tumor suppressor by SMYD2. J. Biol. Chem., 2010, 285(48), 37733-37740.
[http://dx.doi.org/10.1074/jbc.M110.137612] [PMID: 20870719]
[27]
Arrowsmith, C.H.; Bountra, C.; Fish, P.V.; Lee, K.; Schapira, M. Epigenetic protein families: A new frontier for drug discovery. Nat. Rev. Drug Discov., 2012, 11(5), 384-400.
[http://dx.doi.org/10.1038/nrd3674] [PMID: 22498752]
[28]
Ambler, R.P.; Rees, M.W. Epsilon-N-Methyl-lysine in bacterial flagellar protein. Nature, 1959, 184(4679), 56-57.
[http://dx.doi.org/10.1038/184056b0] [PMID: 13793118]
[29]
Murray, K. The occurrance of epsilon-N-methyl lysine in histones. Biochemistry, 1964, 3(1), 10-15.
[http://dx.doi.org/10.1021/bi00889a003] [PMID: 14114491]
[30]
Carlson, S.M.; Gozani, O. Nonhistone lysine methylation in the regulation of cancer pathways. Cold Spring Harb. Perspect. Med., 2016, 6(11), a026435.
[http://dx.doi.org/10.1101/cshperspect.a026435] [PMID: 27580749]
[31]
Clarke, S.G. Protein methylation at the surface and buried deep: Thinking outside the histone box. Trends Biochem. Sci., 2013, 38(5), 243-252.
[http://dx.doi.org/10.1016/j.tibs.2013.02.004] [PMID: 23490039]
[32]
Cao, X. J.; Garcia, B. A. Global proteomics analysis of protein lysine methylation. Curr. Protoc. Protein Sci., 2016, 86, 24.8.1-24.8.19.
[http://dx.doi.org/10.1002/cpps.16]
[33]
Hamamoto, R.; Saloura, V.; Nakamura, Y. Critical roles of non-histone protein lysine methylation in human tumorigenesis. Nat. Rev. Cancer, 2015, 15(2), 110-124.
[http://dx.doi.org/10.1038/nrc3884] [PMID: 25614009]
[34]
Mazur, P.K.; Reynoird, N.; Khatri, P.; Jansen, P.W.T.C.; Wilkinson, A.W.; Liu, S.; Barbash, O.; Van Aller, G.S.; Huddleston, M.; Dhanak, D.; Tummino, P.J.; Kruger, R.G.; Garcia, B.A.; Butte, A.J.; Vermeulen, M.; Sage, J.; Gozani, O. SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer. Nature, 2014, 510(7504), 283-287.
[http://dx.doi.org/10.1038/nature13320] [PMID: 24847881]
[35]
Wagner, T.; Jung, M. New lysine methyltransferase drug targets in cancer. Nat. Biotechnol., 2012, 30(7), 622-623.
[http://dx.doi.org/10.1038/nbt.2300] [PMID: 22781684]
[36]
Husmann, D.; Gozani, O. Histone lysine methyltransferases in biology and disease. Nat. Struct. Mol. Biol., 2019, 26(10), 880-889.
[http://dx.doi.org/10.1038/s41594-019-0298-7] [PMID: 31582846]
[37]
Jenuwein, T.; Laible, G.; Dorn, R.; Reuter, G. SET domain proteins modulate chromatin domains in eu- and heterochromatin. Cell. Mol. Life Sci., 1998, 54(1), 80-93.
[http://dx.doi.org/10.1007/s000180050127] [PMID: 9487389]
[38]
Cheng, X.; Collins, R.E.; Zhang, X. Structural and sequence motifs of protein (histone) methylation enzymes. Annu. Rev. Biophys. Biomol. Struct., 2005, 34(1), 267-294.
[http://dx.doi.org/10.1146/annurev.biophys.34.040204.144452] [PMID: 15869391]
[39]
Allis, C.D.; Berger, S.L.; Cote, J.; Dent, S.; Jenuwien, T.; Kouzarides, T.; Pillus, L.; Reinberg, D.; Shi, Y.; Shiekhattar, R.; Shilatifard, A.; Workman, J.; Zhang, Y. New nomenclature for chromatin-modifying enzymes. Cell, 2007, 131(4), 633-636.
[http://dx.doi.org/10.1016/j.cell.2007.10.039] [PMID: 18022353]
[40]
Zhang, X.; Tamaru, H.; Khan, S.I.; Horton, J.R.; Keefe, L.J.; Selker, E.U.; Cheng, X. Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase. Cell, 2002, 111(1), 117-127.
[http://dx.doi.org/10.1016/S0092-8674(02)00999-6] [PMID: 12372305]
[41]
Jacobs, S.A.; Harp, J.M.; Devarakonda, S.; Kim, Y.; Rastinejad, F.; Khorasanizadeh, S. The active site of the SET domain is constructed on a knot. Nat. Struct. Biol., 2002, 9(11), 833-838.
[http://dx.doi.org/10.1038/nsb861] [PMID: 12389038]
[42]
Taverna, S.D.; Li, H.; Ruthenburg, A.J.; Allis, C.D.; Patel, D.J. How chromatin-binding modules interpret histone modifications: Lessons from professional pocket pickers. Nat. Struct. Mol. Biol., 2007, 14(11), 1025-1040.
[http://dx.doi.org/10.1038/nsmb1338] [PMID: 17984965]
[43]
Bannister, A.J.; Kouzarides, T. Regulation of chromatin by histone modifications. Cell Res., 2011, 21(3), 381-395.
[http://dx.doi.org/10.1038/cr.2011.22] [PMID: 21321607]
[44]
Barski, A.; Cuddapah, S.; Cui, K.; Roh, T.Y.; Schones, D.E.; Wang, Z.; Wei, G.; Chepelev, I.; Zhao, K. High-resolution profiling of histone methylations in the human genome. Cell, 2007, 129(4), 823-837.
[http://dx.doi.org/10.1016/j.cell.2007.05.009] [PMID: 17512414]
[45]
Zhang, Z.; Pugh, B.F. High-resolution genome-wide mapping of the primary structure of chromatin. Cell, 2011, 144(2), 175-186.
[http://dx.doi.org/10.1016/j.cell.2011.01.003] [PMID: 21241889]
[46]
Cho, H.S.; Shimazu, T.; Toyokawa, G.; Daigo, Y.; Maehara, Y.; Hayami, S.; Ito, A.; Masuda, K.; Ikawa, N.; Field, H.I.; Tsuchiya, E.; Ohnuma, S.; Ponder, B.A.J.; Yoshida, M.; Nakamura, Y.; Hamamoto, R. Enhanced HSP70 lysine methylation promotes proliferation of cancer cells through activation of Aurora kinase B. Nat. Commun., 2012, 3(1), 1072.
[http://dx.doi.org/10.1038/ncomms2074] [PMID: 22990868]
[47]
Cho, H.S.; Hayami, S.; Toyokawa, G.; Maejima, K.; Yamane, Y.; Suzuki, T.; Dohmae, N.; Kogure, M.; Kang, D.; Neal, D.E.; Ponder, B.A.J.; Yamaue, H.; Nakamura, Y.; Hamamoto, R. RB1 methylation by SMYD2 enhances cell cycle progression through an increase of RB1 phosphorylation. Neoplasia, 2012, 14(6), 476-IN8.
[http://dx.doi.org/10.1593/neo.12656] [PMID: 22787429]
[48]
Hamamoto, R.; Toyokawa, G.; Nakakido, M.; Ueda, K.; Nakamura, Y. SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by regulating the chaperone complex formation. Cancer Lett., 2014, 351(1), 126-133.
[http://dx.doi.org/10.1016/j.canlet.2014.05.014] [PMID: 24880080]
[49]
Kunizaki, M.; Hamamoto, R.; Silva, F.P.; Yamaguchi, K.; Nagayasu, T.; Shibuya, M.; Nakamura, Y.; Furukawa, Y. The lysine 831 of vascular endothelial growth factor receptor 1 is a novel target of methylation by SMYD3. Cancer Res., 2007, 67(22), 10759-10765.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-1132] [PMID: 18006819]
[50]
Nakamura, Y. Isolation of p53-target genes and their functional analysis. Cancer Sci., 2004, 95(1), 7-11.
[http://dx.doi.org/10.1111/j.1349-7006.2004.tb03163.x] [PMID: 14720320]
[51]
Huang, J.; Dorsey, J.; Chuikov, S.; Zhang, X.; Jenuwein, T.; Reinberg, D.; Berger, S.L. G9a and Glp methylate lysine 373 in the tumor suppressor p53. J. Biol. Chem., 2010, 285(13), 9636-9641.
[http://dx.doi.org/10.1074/jbc.M109.062588] [PMID: 20118233]
[52]
Goodrich, D.W. The retinoblastoma tumor-suppressor gene, the exception that proves the rule. Oncogene, 2006, 25(38), 5233-5243.
[http://dx.doi.org/10.1038/sj.onc.1209616] [PMID: 16936742]
[53]
Chen, H.Z.; Tsai, S.Y.; Leone, G. Emerging roles of E2Fs in cancer: An exit from cell cycle control. Nat. Rev. Cancer, 2009, 9(11), 785-797.
[http://dx.doi.org/10.1038/nrc2696] [PMID: 19851314]
[54]
Kontaki, H.; Talianidis, I. Lysine methylation regulates E2F1-induced cell death. Mol. Cell, 2010, 39(1), 152-160.
[http://dx.doi.org/10.1016/j.molcel.2010.06.006] [PMID: 20603083]
[55]
Ciocca, D.R.; Calderwood, S.K. Heat shock proteins in cancer: Diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones, 2005, 10(2), 86-103.
[http://dx.doi.org/10.1379/CSC-99r.1] [PMID: 16038406]
[56]
Trepel, J.; Mollapour, M.; Giaccone, G.; Neckers, L. Targeting the dynamic HSP90 complex in cancer. Nat. Rev. Cancer, 2010, 10(8), 537-549.
[http://dx.doi.org/10.1038/nrc2887] [PMID: 20651736]
[57]
Whitesell, L.; Lindquist, S.L. HSP90 and the chaperoning of cancer. Nat. Rev. Cancer, 2005, 5(10), 761-772.
[http://dx.doi.org/10.1038/nrc1716] [PMID: 16175177]
[58]
Li, Y.; Liu, C.F.; Rao, G.W. A review on poly (ADP-ribose) polymerase (PARP) inhibitors and synthetic methodologies. Curr. Med. Chem., 2021, 28(8), 1565-1584.
[http://dx.doi.org/10.2174/0929867327666200312113011] [PMID: 32164505]
[59]
Chen, A. PARP inhibitors: Its role in treatment of cancer. Chin. J. Cancer, 2011, 30(7), 463-471.
[http://dx.doi.org/10.5732/cjc.011.10111] [PMID: 21718592]
[60]
Piao, L.; Kang, D.; Suzuki, T.; Masuda, A.; Dohmae, N.; Nakamura, Y.; Hamamoto, R. The histone methyltransferase SMYD2 methylates PARP1 and promotes poly(ADP-ribosyl)ation activity in cancer cells. Neoplasia, 2014, 16(3), 257-64.
[http://dx.doi.org/10.1016/j.neo.2014.03.002]
[61]
Kukita, A.; Sone, K.; Oda, K.; Hamamoto, R.; Kaneko, S.; Komatsu, M.; Wada, M.; Honjoh, H.; Kawata, Y.; Kojima, M.; Oki, S.; Sato, M.; Asada, K.; Taguchi, A.; Miyasaka, A.; Tanikawa, M.; Nagasaka, K.; Matsumoto, Y.; Wada-Hiraike, O.; Osuga, Y.; Fujii, T. Histone methyltransferase SMYD2 selective inhibitor LLY-507 in combination with poly ADP ribose polymerase inhibitor has therapeutic potential against high-grade serous ovarian carcinomas. Biochem. Biophys. Res. Commun., 2019, 513(2), 340-346.
[http://dx.doi.org/10.1016/j.bbrc.2019.03.155] [PMID: 30955858]
[62]
Chi, P.; Allis, C.D.; Wang, G.G. Covalent histone modifications — miswritten, misinterpreted and mis-erased in human cancers. Nat. Rev. Cancer, 2010, 10(7), 457-469.
[http://dx.doi.org/10.1038/nrc2876] [PMID: 20574448]
[63]
Morin, R.D.; Johnson, N.A.; Severson, T.M.; Mungall, A.J.; An, J.; Goya, R.; Paul, J.E.; Boyle, M.; Woolcock, B.W.; Kuchenbauer, F.; Yap, D.; Humphries, R.K.; Griffith, O.L.; Shah, S.; Zhu, H.; Kimbara, M.; Shashkin, P.; Charlot, J.F.; Tcherpakov, M.; Corbett, R.; Tam, A.; Varhol, R.; Smailus, D.; Moksa, M.; Zhao, Y.; Delaney, A.; Qian, H.; Birol, I.; Schein, J.; Moore, R.; Holt, R.; Horsman, D.E.; Connors, J.M.; Jones, S.; Aparicio, S.; Hirst, M.; Gascoyne, R.D.; Marra, M.A. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat. Genet., 2010, 42(2), 181-185.
[http://dx.doi.org/10.1038/ng.518] [PMID: 20081860]
[64]
Morin, R.D.; Mendez-Lago, M.; Mungall, A.J.; Goya, R.; Mungall, K.L.; Corbett, R.D.; Johnson, N.A.; Severson, T.M.; Chiu, R.; Field, M.; Jackman, S.; Krzywinski, M.; Scott, D.W.; Trinh, D.L.; Tamura-Wells, J.; Li, S.; Firme, M.R.; Rogic, S.; Griffith, M.; Chan, S.; Yakovenko, O.; Meyer, I.M.; Zhao, E.Y.; Smailus, D.; Moksa, M.; Chittaranjan, S.; Rimsza, L.; Brooks-Wilson, A.; Spinelli, J.J.; Ben-Neriah, S.; Meissner, B.; Woolcock, B.; Boyle, M.; McDonald, H.; Tam, A.; Zhao, Y.; Delaney, A.; Zeng, T.; Tse, K.; Butterfield, Y.; Birol, I.; Holt, R.; Schein, J.; Horsman, D.E.; Moore, R.; Jones, S.J.M.; Connors, J.M.; Hirst, M.; Gascoyne, R.D.; Marra, M.A. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature, 2011, 476(7360), 298-303.
[http://dx.doi.org/10.1038/nature10351] [PMID: 21796119]
[65]
Lohr, J.G.; Stojanov, P.; Lawrence, M.S.; Auclair, D.; Chapuy, B.; Sougnez, C.; Cruz-Gordillo, P.; Knoechel, B.; Asmann, Y.W.; Slager, S.L.; Novak, A.J.; Dogan, A.; Ansell, S.M.; Link, B.K.; Zou, L.; Gould, J.; Saksena, G.; Stransky, N.; Rangel-Escareño, C.; Fernandez-Lopez, J.C.; Hidalgo-Miranda, A.; Melendez-Zajgla, J.; Hernández-Lemus, E.; Schwarz-Cruz y Celis, A.; Imaz-Rosshandler, I.; Ojesina, A.I.; Jung, J.; Pedamallu, C.S.; Lander, E.S.; Habermann, T.M.; Cerhan, J.R.; Shipp, M.A.; Getz, G.; Golub, T.R. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc. Natl. Acad. Sci. USA, 2012, 109(10), 3879-3884.
[http://dx.doi.org/10.1073/pnas.1121343109] [PMID: 22343534]
[66]
Chesi, M.; Nardini, E.; Lim, R.S.C.; Smith, K.D.; Kuehl, W.M.; Bergsagel, P.L. The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts. Blood, 1998, 92(9), 3025-3034.
[http://dx.doi.org/10.1182/blood.V92.9.3025] [PMID: 9787135]
[67]
Bergsagel, P.L.; Kuehl, W.M. Molecular pathogenesis and a consequent classification of multiple myeloma. J. Clin. Oncol., 2005, 23(26), 6333-6338.
[http://dx.doi.org/10.1200/JCO.2005.05.021] [PMID: 16155016]
[68]
Peters, A.H.F.M.; O’Carroll, D.; Scherthan, H.; Mechtler, K.; Sauer, S.; Schöfer, C.; Weipoltshammer, K.; Pagani, M.; Lachner, M.; Kohlmaier, A.; Opravil, S.; Doyle, M.; Sibilia, M.; Jenuwein, T. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell, 2001, 107(3), 323-337.
[http://dx.doi.org/10.1016/S0092-8674(01)00542-6] [PMID: 11701123]
[69]
Hess, J.L. Mechanisms of transformation by MLL. Crit. Rev. Eukaryot. Gene Expr., 2004, 14(4), 235-254.
[http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.v14.i4.10] [PMID: 15663355]
[70]
Ballabio, E.; Milne, T.A. Molecular and Epigenetic Mechanisms of MLL in human leukemogenesis. Cancers (Basel), 2012, 4(3), 904-944.
[http://dx.doi.org/10.3390/cancers4030904] [PMID: 24213472]
[71]
Natarajan, T.G.; Kallakury, B.V.; Sheehan, C.E.; Bartlett, M.B.; Ganesan, N.; Preet, A.; Ross, J.S.; FitzGerald, K.T. Epigenetic regulator MLL2 shows altered expression in cancer cell lines and tumors from human breast and colon. Cancer Cell Int., 2010, 10(1), 13.
[http://dx.doi.org/10.1186/1475-2867-10-13] [PMID: 20433758]
[72]
Komatsu, S.; Imoto, I.; Tsuda, H.; Kozaki, K.; Muramatsu, T.; Shimada, Y.; Aiko, S.; Yoshizumi, Y.; Ichikawa, D.; Otsuji, E.; Inazawa, J. Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma. Carcinogenesis, 2009, 30(7), 1139-1146.
[http://dx.doi.org/10.1093/carcin/bgp116] [PMID: 19423649]
[73]
Reynoird, N.; Mazur, P.K.; Stellfeld, T.; Flores, N.M.; Lofgren, S.M.; Carlson, S.M.; Brambilla, E.; Hainaut, P.; Kaznowska, E.B.; Arrowsmith, C.H.; Khatri, P.; Stresemann, C.; Gozani, O.; Sage, J. Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer. Genes Dev., 2016, 30(7), 772-785.
[http://dx.doi.org/10.1101/gad.275529.115] [PMID: 26988419]
[74]
Li, L.X.; Zhou, J.X.; Calvet, J.P.; Godwin, A.K.; Jensen, R.A.; Li, X. Lysine methyltransferase SMYD2 promotes triple negative breast cancer progression. Cell Death Dis., 2018, 9(3), 326.
[http://dx.doi.org/10.1038/s41419-018-0347-x] [PMID: 29487338]
[75]
Cock-Rada, A.M.; Medjkane, S.; Janski, N.; Yousfi, N.; Perichon, M.; Chaussepied, M.; Chluba, J.; Langsley, G.; Weitzman, J.B. SMYD3 promotes cancer invasion by epigenetic upregulation of the metalloproteinase MMP-9. Cancer Res., 2012, 72(3), 810-820.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1052] [PMID: 22194464]
[76]
Hamamoto, R.; Furukawa, Y.; Morita, M.; Iimura, Y.; Silva, F.P.; Li, M.; Yagyu, R.; Nakamura, Y. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat. Cell Biol., 2004, 6(8), 731-740.
[http://dx.doi.org/10.1038/ncb1151] [PMID: 15235609]
[77]
Dong, S.W.; Zhang, H.; Wang, B.L.; Sun, P.; Wang, Y.G.; Zhang, P. Effect of the downregulation of SMYD3 expression by RNAi on RIZ1 expression and proliferation of esophageal squamous cell carcinoma. Oncol. Rep., 2014, 32(3), 1064-1070.
[http://dx.doi.org/10.3892/or.2014.3307] [PMID: 24993551]
[78]
Wang, L.; Wang, Q.T.; Liu, Y.P.; Dong, Q.Q.; Hu, H.J.; Miao, Z.; Li, S.; Liu, Y.; Zhou, H.; Zhang, T.C.; Ma, W.J.; Luo, X.G. ATM signaling pathway is implicated in the SMYD3-mediated proliferation and migration of gastric cancer cells. J. Gastric Cancer, 2017, 17(4), 295-305.
[http://dx.doi.org/10.5230/jgc.2017.17.e33] [PMID: 29302370]
[79]
Luo, X.G.; Ding, Y.; Zhou, Q.F.; Ye, L.; Wang, S.Z.; Xi, T. SET and MYND domain-containing protein 3 decreases sensitivity to dexamethasone and stimulates cell adhesion and migration in NIH3T3 cells. J. Biosci. Bioeng., 2007, 103(5), 444-450.
[http://dx.doi.org/10.1263/jbb.103.444] [PMID: 17609160]
[80]
Tsuge, M.; Hamamoto, R.; Silva, F.P.; Ohnishi, Y.; Chayama, K.; Kamatani, N.; Furukawa, Y.; Nakamura, Y. A variable number of tandem repeats polymorphism in an E2F-1 binding element in the 5′ flanking region of SMYD3 is a risk factor for human cancers. Nat. Genet., 2005, 37(10), 1104-1107.
[http://dx.doi.org/10.1038/ng1638] [PMID: 16155568]
[81]
Zheng, W.; Ibáñez, G.; Wu, H.; Blum, G.; Zeng, H.; Dong, A.; Li, F.; Hajian, T.; Allali-Hassani, A.; Amaya, M.F.; Siarheyeva, A.; Yu, W.; Brown, P.J.; Schapira, M.; Vedadi, M.; Min, J.; Luo, M. Sinefungin derivatives as inhibitors and structure probes of protein lysine methyltransferase SETD2. J. Am. Chem. Soc., 2012, 134(43), 18004-18014.
[http://dx.doi.org/10.1021/ja307060p] [PMID: 23043551]
[82]
Newbold, R.F.; Mokbel, K. Evidence for a tumour suppressor function of SETD2 in human breast cancer: A new hypothesis. Anticancer Res., 2010, 30(9), 3309-3311.
[PMID: 20944102]
[83]
Barsyte-Lovejoy, D.; Li, F.; Oudhoff, M.J.; Tatlock, J.H.; Dong, A.; Zeng, H.; Wu, H.; Freeman, S.A.; Schapira, M.; Senisterra, G.A.; Kuznetsova, E.; Marcellus, R.; Allali-Hassani, A.; Kennedy, S.; Lambert, J.P.; Couzens, A.L.; Aman, A.; Gingras, A.C.; Al-Awar, R.; Fish, P.V.; Gerstenberger, B.S.; Roberts, L.; Benn, C.L.; Grimley, R.L.; Braam, M.J.S.; Rossi, F.M.V.; Sudol, M.; Brown, P.J.; Bunnage, M.E.; Owen, D.R.; Zaph, C.; Vedadi, M.; Arrowsmith, C.H. ( R )-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Proc. Natl. Acad. Sci. USA, 2014, 111(35), 12853-12858.
[http://dx.doi.org/10.1073/pnas.1407358111] [PMID: 25136132]
[84]
Subramanian, K.; Jia, D.; Kapoor-Vazirani, P.; Powell, D.R.; Collins, R.E.; Sharma, D.; Peng, J.; Cheng, X.; Vertino, P.M. Regulation of estrogen receptor alpha by the SET7 lysine methyltransferase. Mol. Cell, 2008, 30(3), 336-347.
[http://dx.doi.org/10.1016/j.molcel.2008.03.022] [PMID: 18471979]
[85]
Takawa, M.; Cho, H.S.; Hayami, S.; Toyokawa, G.; Kogure, M.; Yamane, Y.; Iwai, Y.; Maejima, K.; Ueda, K.; Masuda, A.; Dohmae, N.; Field, H.I.; Tsunoda, T.; Kobayashi, T.; Akasu, T.; Sugiyama, M.; Ohnuma, S.; Atomi, Y.; Ponder, B.A.J.; Nakamura, Y.; Hamamoto, R. Histone lysine methyltransferase SETD8 promotes carcinogenesis by deregulating PCNA expression. Cancer Res., 2012, 72(13), 3217-3227.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-3701] [PMID: 22556262]
[86]
Sakamoto, L.H.T.; Andrade, R.V.; Felipe, M.S.S.; Motoyama, A.B.; Pittella Silva, F. SMYD2 is highly expressed in pediatric acute lymphoblastic leukemia and constitutes a bad prognostic factor. Leuk. Res., 2014, 38(4), 496-502.
[http://dx.doi.org/10.1016/j.leukres.2014.01.013] [PMID: 24631370]
[87]
Li, B.; Liu, H.Y.; Guo, S.H.; Sun, P.; Gong, F.M.; Jia, B.Q. Association of MLL3 expression with prognosis in gastric cancer. Genet. Mol. Res., 2014, 13(3), 7513-7518.
[http://dx.doi.org/10.4238/2014.September.12.18] [PMID: 25222251]
[88]
Ruault, M.; Brun, M.E.; Ventura, M.; Roizès, G.; De Sario, A. MLL3, a new human member of the TRX/MLL gene family, maps to 7q36, a chromosome region frequently deleted in myeloid leukaemia. Gene, 2002, 284(1-2), 73-81.
[http://dx.doi.org/10.1016/S0378-1119(02)00392-X] [PMID: 11891048]
[89]
Spyropoulou, A.; Gargalionis, A.; Dalagiorgou, G.; Adamopoulos, C.; Papavassiliou, K.A.; Lea, R.W.; Piperi, C.; Papavassiliou, A.G. Role of histone lysine methyltransferases SUV39H1 and SETDB1 in gliomagenesis: Modulation of cell proliferation, migration, and colony formation. Neuromolecular Med., 2014, 16(1), 70-82.
[http://dx.doi.org/10.1007/s12017-013-8254-x] [PMID: 23943221]
[90]
O’Carroll, D.; Scherthan, H.; Peters, A.H.F.M.; Opravil, S.; Haynes, A.R.; Laible, G.; Rea, S.; Schmid, M.; Lebersorger, A.; Jerratsch, M.; Sattler, L.; Mattei, M.G.; Denny, P.; Brown, S.D.M.; Schweizer, D.; Jenuwein, T. Isolation and characterization of Suv39h2, a second histone H3 methyltransferase gene that displays testis-specific expression. Mol. Cell. Biol., 2000, 20(24), 9423-9433.
[http://dx.doi.org/10.1128/MCB.20.24.9423-9433.2000] [PMID: 11094092]
[91]
Goyama, S.; Nitta, E.; Yoshino, T.; Kako, S.; Watanabe-Okochi, N.; Shimabe, M.; Imai, Y.; Takahashi, K.; Kurokawa, M. EVI-1 interacts with histone methyltransferases SUV39H1 and G9a for transcriptional repression and bone marrow immortalization. Leukemia, 2010, 24(1), 81-88.
[http://dx.doi.org/10.1038/leu.2009.202] [PMID: 19776757]
[92]
Wang, G.G.; Cai, L.; Pasillas, M.P.; Kamps, M.P. NUP98–NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis. Nat. Cell Biol., 2007, 9(7), 804-812.
[http://dx.doi.org/10.1038/ncb1608] [PMID: 17589499]
[93]
Ezponda, T.; Popovic, R.; Shah, M.Y.; Martinez-Garcia, E.; Zheng, Y.; Min, D-J.; Will, C.; Neri, A.; Kelleher, N.L.; Yu, J.; Licht, J.D. The histone methyltransferase MMSET/WHSC1 activates TWIST1 to promote an epithelial–mesenchymal transition and invasive properties of prostate cancer. Oncogene, 2013, 32(23), 2882-2890.
[http://dx.doi.org/10.1038/onc.2012.297] [PMID: 22797064]
[94]
Kim, J.Y.; Kee, H.J.; Choe, N.W.; Kim, S.M.; Eom, G.H.; Baek, H.J.; Kook, H.; Kook, H.; Seo, S.B. Multiple-myeloma-related WHSC1/MMSET isoform RE-IIBP is a histone methyltransferase with transcriptional repression activity. Mol. Cell. Biol., 2008, 28(6), 2023-2034.
[http://dx.doi.org/10.1128/MCB.02130-07] [PMID: 18172012]
[95]
Zhou, Z.; Thomsen, R.; Kahns, S.; Nielsen, A.L. The NSD3L histone methyltransferase regulates cell cycle and cell invasion in breast cancer cells. Biochem. Biophys. Res. Commun., 2010, 398(3), 565-570.
[http://dx.doi.org/10.1016/j.bbrc.2010.06.119] [PMID: 20599755]
[96]
Kang, D.; Cho, H.S.; Toyokawa, G.; Kogure, M.; Yamane, Y.; Iwai, Y.; Hayami, S.; Tsunoda, T.; Field, H.I.; Matsuda, K.; Neal, D.E.; Ponder, B.A.J.; Maehara, Y.; Nakamura, Y.; Hamamoto, R. The histone methyltransferase Wolf–Hirschhorn syndrome candidate 1-like 1 (WHSC1L1) is involved in human carcinogenesis. Genes Chromosomes Cancer, 2013, 52(2), 126-139.
[http://dx.doi.org/10.1002/gcc.22012] [PMID: 23011637]
[97]
Bracken, A.P.; Pasini, D.; Capra, M.; Prosperini, E.; Colli, E.; Helin, K. EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J., 2003, 22(20), 5323-5335.
[http://dx.doi.org/10.1093/emboj/cdg542] [PMID: 14532106]
[98]
Kleer, C.G.; Cao, Q.; Varambally, S.; Shen, R.; Ota, I.; Tomlins, S.A.; Ghosh, D.; Sewalt, R.G.A.B.; Otte, A.P.; Hayes, D.F.; Sabel, M.S.; Livant, D.; Weiss, S.J.; Rubin, M.A.; Chinnaiyan, A.M. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc. Natl. Acad. Sci. USA, 2003, 100(20), 11606-11611.
[http://dx.doi.org/10.1073/pnas.1933744100] [PMID: 14500907]
[99]
Bernt, K.M.; Armstrong, S.A. A role for DOT1L in MLL -rearranged leukemias. Epigenomics, 2011, 3(6), 667-670.
[http://dx.doi.org/10.2217/epi.11.98] [PMID: 22126283]
[100]
de Almeida, S.F.; Grosso, A.R.; Koch, F.; Fenouil, R.; Carvalho, S.; Andrade, J.; Levezinho, H.; Gut, M.; Eick, D.; Gut, I.; Andrau, J.C.; Ferrier, P.; Carmo-Fonseca, M. Splicing enhances recruitment of methyltransferase HYPB/Setd2 and methylation of histone H3 Lys36. Nat. Struct. Mol. Biol., 2011, 18(9), 977-983.
[http://dx.doi.org/10.1038/nsmb.2123] [PMID: 21792193]
[101]
Hu, M.; Sun, X.J.; Zhang, Y.L.; Kuang, Y.; Hu, C.Q.; Wu, W.L.; Shen, S.H.; Du, T.T.; Li, H.; He, F.; Xiao, H.S.; Wang, Z.G.; Liu, T.X.; Lu, H.; Huang, Q.H.; Chen, S.J.; Chen, Z. Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling. Proc. Natl. Acad. Sci. USA, 2010, 107(7), 2956-2961.
[http://dx.doi.org/10.1073/pnas.0915033107] [PMID: 20133625]
[102]
Duns, G.; van den Berg, E.; van Duivenbode, I.; Osinga, J.; Hollema, H.; Hofstra, R.M.W.; Kok, K. Histone methyltransferase gene SETD2 is a novel tumor suppressor gene in clear cell renal cell carcinoma. Cancer Res., 2010, 70(11), 4287-4291.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-0120] [PMID: 20501857]
[103]
Gossage, L.; Murtaza, M.; Slatter, A.F.; Lichtenstein, C.P.; Warren, A.; Haynes, B.; Marass, F.; Roberts, I.; Shanahan, S.J.; Claas, A.; Dunham, A.; May, A.P.; Rosenfeld, N.; Forshew, T.; Eisen, T. Clinical and pathological impact of VHL, PBRM1, BAP1, SETD2, KDM6A, and JARID1c in clear cell renal cell carcinoma. Genes Chromosomes Cancer, 2014, 53(1), 38-51.
[http://dx.doi.org/10.1002/gcc.22116] [PMID: 24166983]
[104]
Hao, C.; Wang, L.; Peng, S.; Cao, M.; Li, H.; Hu, J.; Huang, X.; Liu, W.; Zhang, H.; Wu, S.; Pataer, A.; Heymach, J.V.; Eterovic, A.K.; Zhang, Q.; Shaw, K.R.; Chen, K.; Futreal, A.; Wang, M.; Hofstetter, W.; Mehran, R.; Rice, D.; Roth, J.A.; Sepesi, B.; Swisher, S.G.; Vaporciyan, A.; Walsh, G.L.; Johnson, F.M.; Fang, B. Gene mutations in primary tumors and corresponding patient-derived xenografts derived from non-small cell lung cancer. Cancer Lett., 2015, 357(1), 179-185.
[http://dx.doi.org/10.1016/j.canlet.2014.11.024] [PMID: 25444907]
[105]
Fontebasso, A.M.; Schwartzentruber, J.; Khuong-Quang, D.A.; Liu, X.Y.; Sturm, D.; Korshunov, A.; Jones, D.T.W.; Witt, H.; Kool, M.; Albrecht, S.; Fleming, A.; Hadjadj, D.; Busche, S.; Lepage, P.; Montpetit, A.; Staffa, A.; Gerges, N.; Zakrzewska, M.; Zakrzewski, K.; Liberski, P.P.; Hauser, P.; Garami, M.; Klekner, A.; Bognar, L.; Zadeh, G.; Faury, D.; Pfister, S.M.; Jabado, N.; Majewski, J. Mutations in SETD2 and genes affecting histone H3K36 methylation target hemispheric high-grade gliomas. Acta Neuropathol., 2013, 125(5), 659-669.
[http://dx.doi.org/10.1007/s00401-013-1095-8] [PMID: 23417712]
[106]
Bu, J.; Chen, A.; Yan, X.; He, F.; Dong, Y.; Zhou, Y.; He, J.; Zhan, D.; Lin, P.; Hayashi, Y.; Sun, Y.; Zhang, Y.; Xiao, Z.; Grimes, H.L.; Wang, Q.F.; Huang, G. SETD2- mediated crosstalk between H3K36me3 and H3K79me2 in MLL-rearranged leukemia. Leukemia, 2018, 32(4), 890-899.
[http://dx.doi.org/10.1038/leu.2017.339] [PMID: 29249820]
[107]
Nishioka, K.; Chuikov, S.; Sarma, K.; Erdjument-Bromage, H.; Allis, C.D.; Tempst, P.; Reinberg, D. Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev., 2002, 16(4), 479-489.
[http://dx.doi.org/10.1101/gad.967202] [PMID: 11850410]
[108]
Wang, H.; Cao, R.; Xia, L.; Erdjument-Bromage, H.; Borchers, C.; Tempst, P.; Zhang, Y. Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase. Mol. Cell, 2001, 8(6), 1207-1217.
[http://dx.doi.org/10.1016/S1097-2765(01)00405-1] [PMID: 11779497]
[109]
Pradhan, S.; Chin, H.G.; Estève, P.O.; Jacobsen, S.E. SET7/9 mediated methylation of non-histone proteins in mammalian cells. Epigenetics, 2009, 4(6), 383-387.
[http://dx.doi.org/10.4161/epi.4.6.9450] [PMID: 19684477]
[110]
Carr, S.M.; Munro, S.; Kessler, B.; Oppermann, U.; La Thangue, N.B. Interplay between lysine methylation and Cdk phosphorylation in growth control by the retinoblastoma protein. EMBO J., 2011, 30(2), 317-327.
[http://dx.doi.org/10.1038/emboj.2010.311] [PMID: 21119616]
[111]
Yang, J.; Huang, J.; Dasgupta, M.; Sears, N.; Miyagi, M.; Wang, B.; Chance, M.R.; Chen, X.; Du, Y.; Wang, Y.; An, L.; Wang, Q.; Lu, T.; Zhang, X.; Wang, Z.; Stark, G.R. Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes. Proc. Natl. Acad. Sci. USA, 2010, 107(50), 21499-21504.
[http://dx.doi.org/10.1073/pnas.1016147107] [PMID: 21098664]
[112]
Liu, X.; Chen, Z.; Xu, C.; Leng, X.; Cao, H.; Ouyang, G.; Xiao, W. Repression of hypoxia-inducible factor α signaling by Set7-mediated methylation. Nucleic Acids Res., 2015, 43(10), 5081-5098.
[http://dx.doi.org/10.1093/nar/gkv379] [PMID: 25897119]
[113]
Calnan, D.R.; Webb, A.E.; White, J.L.; Stowe, T.R.; Goswami, T.; Shi, X.; Espejo, A.; Bedford, M.T.; Gozani, O.; Gygi, S.P.; Brunet, A. Methylation by Set9 modulates FoxO3 stability and transcriptional activity. Aging (Albany NY), 2012, 4(7), 462-479.
[http://dx.doi.org/10.18632/aging.100471] [PMID: 22820736]
[114]
Estève, P.O.; Chin, H.G.; Benner, J.; Feehery, G.R.; Samaranayake, M.; Horwitz, G.A.; Jacobsen, S.E.; Pradhan, S. Regulation of DNMT1 stability through SET7-mediated lysine methylation in mammalian cells. Proc. Natl. Acad. Sci. USA, 2009, 106(13), 5076-5081.
[http://dx.doi.org/10.1073/pnas.0810362106] [PMID: 19282482]
[115]
Meng, F.; Cheng, S.; Ding, H.; Liu, S.; Liu, Y.; Zhu, K.; Chen, S.; Lu, J.; Xie, Y.; Li, L.; Liu, R.; Shi, Z.; Zhou, Y.; Liu, Y.C.; Zheng, M.; Jiang, H.; Lu, W.; Liu, H.; Luo, C. Discovery and optimization of novel, selective histone methyltransferase SET7 inhibitors by pharmacophore- and docking-based virtual screening. J. Med. Chem., 2015, 58(20), 8166-8181.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01154] [PMID: 26390175]
[116]
Takemoto, Y.; Ito, A.; Niwa, H.; Okamura, M.; Fujiwara, T.; Hirano, T.; Handa, N.; Umehara, T.; Sonoda, T.; Ogawa, K.; Tariq, M.; Nishino, N.; Dan, S.; Kagechika, H.; Yamori, T.; Yokoyama, S.; Yoshida, M. Identification of cyproheptadine as an inhibitor of SET domain containing lysine methyltransferase 7/9 (Set7/9) that regulates estrogen-dependent transcription. J. Med. Chem., 2016, 59(8), 3650-3660.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01732] [PMID: 27088648]
[117]
Beck, D.B.; Oda, H.; Shen, S.S.; Reinberg, D. PR-Set7 and H4K20me1: At the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription. Genes Dev., 2012, 26(4), 325-337.
[http://dx.doi.org/10.1101/gad.177444.111] [PMID: 22345514]
[118]
Nishioka, K.; Rice, J.C.; Sarma, K.; Erdjument-Bromage, H.; Werner, J.; Wang, Y.; Chuikov, S.; Valenzuela, P.; Tempst, P.; Steward, R.; Lis, J.T.; Allis, C.D.; Reinberg, D. PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. Mol. Cell, 2002, 9(6), 1201-1213.
[http://dx.doi.org/10.1016/S1097-2765(02)00548-8] [PMID: 12086618]
[119]
Fang, J.; Feng, Q.; Ketel, C.S.; Wang, H.; Cao, R.; Xia, L.; Erdjument-Bromage, H.; Tempst, P.; Simon, J.A.; Zhang, Y. Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase. Curr. Biol., 2002, 12(13), 1086-1099.
[http://dx.doi.org/10.1016/S0960-9822(02)00924-7] [PMID: 12121615]
[120]
Jørgensen, S.; Schotta, G.; Sørensen, C.S. Histone H4 Lysine 20 methylation: Key player in epigenetic regulation of genomic integrity. Nucleic Acids Res., 2013, 41(5), 2797-2806.
[http://dx.doi.org/10.1093/nar/gkt012] [PMID: 23345616]
[121]
Brustel, J.; Tardat, M.; Kirsh, O.; Grimaud, C.; Julien, E. Coupling mitosis to DNA replication: The emerging role of the histone H4-lysine 20 methyltransferase PR-Set7. Trends Cell Biol., 2011, 21(8), 452-460.
[http://dx.doi.org/10.1016/j.tcb.2011.04.006] [PMID: 21632252]
[122]
Jørgensen, S.; Elvers, I.; Trelle, M.B.; Menzel, T.; Eskildsen, M.; Jensen, O.N.; Helleday, T.; Helin, K.; Sørensen, C.S. The histone methyltransferase SET8 is required for S-phase progression. J. Cell Biol., 2007, 179(7), 1337-1345.
[http://dx.doi.org/10.1083/jcb.200706150] [PMID: 18166648]
[123]
Paulsen, R.D.; Soni, D.V.; Wollman, R.; Hahn, A.T.; Yee, M.C.; Guan, A.; Hesley, J.A.; Miller, S.C.; Cromwell, E.F.; Solow-Cordero, D.E.; Meyer, T.; Cimprich, K.A. A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Mol. Cell, 2009, 35(2), 228-239.
[http://dx.doi.org/10.1016/j.molcel.2009.06.021] [PMID: 19647519]
[124]
Williams, D.E.; Dalisay, D.S.; Li, F.; Amphlett, J.; Maneerat, W.; Chavez, M.A.G.; Wang, Y.A.; Matainaho, T.; Yu, W.; Brown, P.J.; Arrowsmith, C.H.; Vedadi, M.; Andersen, R.J. Nahuoic acid A produced by a Streptomyces sp. isolated from a marine sediment is a selective SAM-competitive inhibitor of the histone methyltransferase SETD8. Org. Lett., 2013, 15(2), 414-417.
[http://dx.doi.org/10.1021/ol303416k] [PMID: 23272941]
[125]
Williams, D.E.; Izard, F.; Arnould, S.; Dalisay, D.S.; Tantapakul, C.; Maneerat, W.; Matainaho, T.; Julien, E.; Andersen, R.J. Structures of nahuoic acids B–E produced in culture by a Streptomyces sp. isolated from a marine sediment and evidence for the inhibition of the histone methyl transferase SETD8 in human cancer cells by nahuoic acid A. J. Org. Chem., 2016, 81(4), 1324-1332.
[http://dx.doi.org/10.1021/acs.joc.5b02569] [PMID: 26815947]
[126]
Ma, A.; Yu, W.; Li, F.; Bleich, R.M.; Herold, J.M.; Butler, K.V.; Norris, J.L.; Korboukh, V.; Tripathy, A.; Janzen, W.P.; Arrowsmith, C.H.; Frye, S.V.; Vedadi, M.; Brown, P.J.; Jin, J. Discovery of a selective, substrate-competitive inhibitor of the lysine methyltransferase SETD8. J. Med. Chem., 2014, 57(15), 6822-6833.
[http://dx.doi.org/10.1021/jm500871s] [PMID: 25032507]
[127]
Ma, A.; Yu, W.; Xiong, Y.; Butler, K.V.; Brown, P.J.; Jin, J. Structure–activity relationship studies of SETD8 inhibitors. MedChemComm, 2014, 5(12), 1892-1898.
[http://dx.doi.org/10.1039/C4MD00317A] [PMID: 25554733]
[128]
Butler, K.V.; Ma, A.; Yu, W.; Li, F.; Tempel, W.; Babault, N.; Pittella-Silva, F.; Shao, J.; Wang, J.; Luo, M.; Vedadi, M.; Brown, P.J.; Arrowsmith, C.H.; Jin, J. Structure-based design of a covalent inhibitor of the SET Domain-Containing Protein 8 (SETD8) Lysine Methyltransferase. J. Med. Chem., 2016, 59(21), 9881-9889.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01244] [PMID: 27804297]
[129]
Blum, G.; Ibáñez, G.; Rao, X.; Shum, D.; Radu, C.; Djaballah, H.; Rice, J.C.; Luo, M. Small-molecule inhibitors of SETD8 with cellular activity. ACS Chem. Biol., 2014, 9(11), 2471-2478.
[http://dx.doi.org/10.1021/cb500515r] [PMID: 25137013]
[130]
Judge, R.A.; Zhu, H.; Upadhyay, A.K.; Bodelle, P.M.; Hutchins, C.W.; Torrent, M.; Marin, V.L.; Yu, W.; Vedadi, M.; Li, F.; Brown, P.J.; Pappano, W.N.; Sun, C.; Petros, A.M. Turning a substrate peptide into a potent inhibitor for the histone methyltransferase SETD8. ACS Med. Chem. Lett., 2016, 7(12), 1102-1106.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00303] [PMID: 27994746]
[131]
Leinhart, K.; Brown, M. SET/MYND lysine methyltransferases regulate gene transcription and protein activity. Genes (Basel), 2011, 2(1), 210-218.
[http://dx.doi.org/10.3390/genes2010210] [PMID: 24710145]
[132]
Spellmon, N.; Holcomb, J.; Trescott, L.; Sirinupong, N.; Yang, Z. Structure and function of SET and MYND domain-containing proteins. Int. J. Mol. Sci., 2015, 16(1), 1406-1428.
[http://dx.doi.org/10.3390/ijms16011406] [PMID: 25580534]
[133]
Fabini, E.; Manoni, E.; Ferroni, C.; Rio, A.D.; Bartolini, M. Small-molecule inhibitors of lysine methyltransferases SMYD2 and SMYD3: Current trends. Future Med. Chem., 2019, 11(8), 901-921.
[http://dx.doi.org/10.4155/fmc-2018-0380] [PMID: 30998113]
[134]
Abu-Farha, M.; Lanouette, S.; Elisma, F.; Tremblay, V.; Butson, J.; Figeys, D.; Couture, J.F. Proteomic analyses of the SMYD family interactomes identify HSP90 as a novel target for SMYD2. J. Mol. Cell Biol., 2011, 3(5), 301-308.
[http://dx.doi.org/10.1093/jmcb/mjr025] [PMID: 22028380]
[135]
Zhang, X.; Tanaka, K.; Yan, J.; Li, J.; Peng, D.; Jiang, Y.; Yang, Z.; Barton, M.C.; Wen, H.; Shi, X. Regulation of estrogen receptor α by histone methyltransferase SMYD2-mediated protein methylation. Proc. Natl. Acad. Sci. USA, 2013, 110(43), 17284-17289.
[http://dx.doi.org/10.1073/pnas.1307959110] [PMID: 24101509]
[136]
Ferguson, A.D.; Larsen, N.A.; Howard, T.; Pollard, H.; Green, I.; Grande, C.; Cheung, T.; Garcia-Arenas, R.; Cowen, S.; Wu, J.; Godin, R.; Chen, H.; Keen, N. Structural basis of substrate methylation and inhibition of SMYD2. Structure, 2011, 19(9), 1262-1273.
[http://dx.doi.org/10.1016/j.str.2011.06.011] [PMID: 21782458]
[137]
Cowen, S.D.; Russell, D.; Dakin, L.A.; Chen, H.; Larsen, N.A.; Godin, R.; Throner, S.; Zheng, X.; Molina, A.; Wu, J.; Cheung, T.; Howard, T.; Garcia-Arenas, R.; Keen, N.; Pendleton, C.S.; Pietenpol, J.A.; Ferguson, A.D. Design, synthesis, and biological activity of substrate competitive SMYD2 inhibitors. J. Med. Chem., 2016, 59(24), 11079-11097.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01303] [PMID: 28002961]
[138]
Sweis, R.F.; Wang, Z.; Algire, M.; Arrowsmith, C.H.; Brown, P.J.; Chiang, G.G.; Guo, J.; Jakob, C.G.; Kennedy, S.; Li, F.; Maag, D.; Shaw, B.; Soni, N.B.; Vedadi, M.; Pappano, W.N. Discovery of A-893, a new cell-active benzoxazinone inhibitor of lysine methyltransferase SMYD2. ACS Med. Chem. Lett., 2015, 6(6), 695-700.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00124] [PMID: 26101576]
[139]
Nguyen, H.; Allali-Hassani, A.; Antonysamy, S.; Chang, S.; Chen, L.H.; Curtis, C.; Emtage, S.; Fan, L.; Gheyi, T.; Li, F.; Liu, S.; Martin, J.R.; Mendel, D.; Olsen, J.B.; Pelletier, L.; Shatseva, T.; Wu, S.; Zhang, F.F.; Arrowsmith, C.H.; Brown, P.J.; Campbell, R.M.; Garcia, B.A.; Barsyte-Lovejoy, D.; Mader, M.; Vedadi, M. LLY-507, a cell-active, potent, and selective inhibitor of protein-lysine methyltransferase SMYD2. J. Biol. Chem., 2015, 290(22), 13641-13653.
[http://dx.doi.org/10.1074/jbc.M114.626861] [PMID: 25825497]
[140]
Eggert, E.; Hillig, R.C.; Koehr, S.; Stöckigt, D.; Weiske, J.; Barak, N.; Mowat, J.; Brumby, T.; Christ, C.D.; ter Laak, A.; Lang, T.; Fernandez-Montalvan, A.E.; Badock, V.; Weinmann, H.; Hartung, I.V.; Barsyte-Lovejoy, D.; Szewczyk, M.; Kennedy, S.; Li, F.; Vedadi, M.; Brown, P.J.; Santhakumar, V.; Arrowsmith, C.H.; Stellfeld, T.; Stresemann, C. Discovery and characterization of a highly potent and selective aminopyrazoline-based in vivo probe (BAY-598) for the protein lysine methyltransferase SMYD2. J. Med. Chem., 2016, 59(10), 4578-4600.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01890] [PMID: 27075367]
[141]
Thomenius, M.J.; Totman, J.; Harvey, D.; Mitchell, L.H.; Riera, T.V.; Cosmopoulos, K.; Grassian, A.R.; Klaus, C.; Foley, M.; Admirand, E.A.; Jahic, H.; Majer, C.; Wigle, T.; Jacques, S.L.; Gureasko, J.; Brach, D.; Lingaraj, T.; West, K.; Smith, S.; Rioux, N.; Waters, N.J.; Tang, C.; Raimondi, A.; Munchhof, M.; Mills, J.E.; Ribich, S.; Porter Scott, M.; Kuntz, K.W.; Janzen, W.P.; Moyer, M.; Smith, J.J.; Chesworth, R.; Copeland, R.A.; Boriack-Sjodin, P.A. Small molecule inhibitors and CRISPR/Cas9 mutagenesis demonstrate that SMYD2 and SMYD3 activity are dispensable for autonomous cancer cell proliferation. PLoS One, 2018, 13(6), e0197372.
[http://dx.doi.org/10.1371/journal.pone.0197372] [PMID: 29856759]
[142]
Van Aller, G.S.; Reynoird, N.; Barbash, O.; Huddleston, M.; Liu, S.; Zmoos, A.F.; McDevitt, P.; Sinnamon, R.; Le, B.; Mas, G.; Annan, R.; Sage, J.; Garcia, B.A.; Tummino, P.J.; Gozani, O.; Kruger, R.G. Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation. Epigenetics, 2012, 7(4), 340-343.
[http://dx.doi.org/10.4161/epi.19506] [PMID: 22419068]
[143]
Vieira, F.Q.; Costa-Pinheiro, P.; Ramalho-Carvalho, J.; Pereira, A.; Menezes, F.D.; Antunes, L.; Carneiro, I.; Oliveira, J.; Henrique, R.; Jerónimo, C. Deregulated expression of selected histone methylases and demethylases in prostate carcinoma. Endocr. Relat. Cancer, 2014, 21(1), 51-61.
[http://dx.doi.org/10.1530/ERC-13-0375] [PMID: 24200674]
[144]
Hamamoto, R.; Silva, F.P.; Tsuge, M.; Nishidate, T.; Katagiri, T.; Nakamura, Y.; Furukawa, Y. Enhanced SMYD3 expression is essential for the growth of breast cancer cells. Cancer Sci., 2006, 97(2), 113-118.
[http://dx.doi.org/10.1111/j.1349-7006.2006.00146.x] [PMID: 16441421]
[145]
Peserico, A.; Germani, A.; Sanese, P.; Barbosa, A.J.; Di Virgilio, V.; Fittipaldi, R.; Fabini, E.; Bertucci, C.; Varchi, G.; Moyer, M.P.; Caretti, G.; Del Rio, A.; Simone, C. A SMYD3 small-molecule inhibitor impairing cancer cell growth. J. Cell. Physiol., 2015, 230(10), 2447-2460.
[http://dx.doi.org/10.1002/jcp.24975] [PMID: 25728514]
[146]
Del Rio, A.; Barbosa, A.J.M.; Caporuscio, F.; Mangiatordi, G.F. CoCoCo: A free suite of multiconformational chemical databases for high-throughput virtual screening purposes. Mol. Biosyst., 2010, 6(11), 2122-2128.
[http://dx.doi.org/10.1039/c0mb00039f] [PMID: 20694263]
[147]
Van Aller, G.S.; Graves, A.P.; Elkins, P.A.; Bonnette, W.G.; McDevitt, P.J.; Zappacosta, F.; Annan, R.S.; Dean, T.W.; Su, D.S.; Carpenter, C.L.; Mohammad, H.P.; Kruger, R.G. Structure-based design of a novel SMYD3 inhibitor that bridges the SAM-and MEKK2-binding pockets. Structure, 2016, 24(5), 774-781.
[http://dx.doi.org/10.1016/j.str.2016.03.010] [PMID: 27066749]
[148]
Mitchell, L.H.; Boriack-Sjodin, P.A.; Smith, S.; Thomenius, M.; Rioux, N.; Munchhof, M.; Mills, J.E.; Klaus, C.; Totman, J.; Riera, T.V.; Raimondi, A.; Jacques, S.L.; West, K.; Foley, M.; Waters, N.J.; Kuntz, K.W.; Wigle, T.J.; Scott, M.P.; Copeland, R.A.; Smith, J.J.; Chesworth, R. Novel oxindole sulfonamides and sulfamides: EPZ031686, the first orally bioavailable small molecule SMYD3 inhibitor. ACS Med. Chem. Lett., 2016, 7(2), 134-138.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00272] [PMID: 26985287]
[149]
Gradl, S.; Steuber, H.; Weiske, J.; Szewczyk, M.M.; Schmees, N.; Siegel, S.; Stoeckigt, D.; Christ, C.D.; Li, F.; Organ, S.; Abbey, M.; Kennedy, S.; Chau, I.; Trush, V.; Barsyte-Lovejoy, D.; Brown, P.J.; Vedadi, M.; Arrowsmith, C.; Husemann, M.; Badock, V.; Bauser, M.; Haegebarth, A.; Hartung, I.V.; Stresemann, C. Discovery of the SMYD3 inhibitor BAY-6035 using thermal shift assay (TSA)-based high-throughput screening. SLAS Discov., 2021, 26(8), 947-960.
[http://dx.doi.org/10.1177/24725552211019409] [PMID: 34154424]
[150]
Tachibana, M.; Sugimoto, K.; Nozaki, M.; Ueda, J.; Ohta, T.; Ohki, M.; Fukuda, M.; Takeda, N.; Niida, H.; Kato, H.; Shinkai, Y. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev., 2002, 16(14), 1779-1791.
[http://dx.doi.org/10.1101/gad.989402] [PMID: 12130538]
[151]
Tachibana, M.; Ueda, J.; Fukuda, M.; Takeda, N.; Ohta, T.; Iwanari, H.; Sakihama, T.; Kodama, T.; Hamakubo, T.; Shinkai, Y. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev., 2005, 19(7), 815-826.
[http://dx.doi.org/10.1101/gad.1284005] [PMID: 15774718]
[152]
Tachibana, M.; Sugimoto, K.; Fukushima, T.; Shinkai, Y. Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J. Biol. Chem., 2001, 276(27), 25309-25317.
[http://dx.doi.org/10.1074/jbc.M101914200] [PMID: 11316813]
[153]
Bittencourt, D.; Wu, D.Y.; Jeong, K.W.; Gerke, D.S.; Herviou, L.; Ianculescu, I.; Chodankar, R.; Siegmund, K.D.; Stallcup, M.R. G9a functions as a molecular scaffold for assembly of transcriptional coactivators on a subset of Glucocorticoid Receptor target genes. Proc. Natl. Acad. Sci. USA, 2012, 109(48), 19673-19678.
[http://dx.doi.org/10.1073/pnas.1211803109] [PMID: 23151507]
[154]
Greiner, D.; Bonaldi, T.; Eskeland, R.; Roemer, E.; Imhof, A. Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3-9. Nat. Chem. Biol., 2005, 1(3), 143-145.
[http://dx.doi.org/10.1038/nchembio721] [PMID: 16408017]
[155]
Iwasa, E.; Hamashima, Y.; Fujishiro, S.; Higuchi, E.; Ito, A.; Yoshida, M.; Sodeoka, M. Total synthesis of (+)-chaetocin and its analogues: Their histone methyltransferase G9a inhibitory activity. J. Am. Chem. Soc., 2010, 132(12), 4078-4079.
[http://dx.doi.org/10.1021/ja101280p] [PMID: 20210309]
[156]
Fujishiro, S.; Dodo, K.; Iwasa, E.; Teng, Y.; Sohtome, Y.; Hamashima, Y.; Ito, A.; Yoshida, M.; Sodeoka, M. Epidithiodiketopiperazine as a pharmacophore for protein lysine methyltransferase G9a inhibitors: Reducing cytotoxicity by structural simplification. Bioorg. Med. Chem. Lett., 2013, 23(3), 733-736.
[http://dx.doi.org/10.1016/j.bmcl.2012.11.087] [PMID: 23266120]
[157]
Cherblanc, F.L.; Chapman, K.L.; Brown, R.; Fuchter, M.J. Chaetocin is a nonspecific inhibitor of histone lysine methyltransferases. Nat. Chem. Biol., 2013, 9(3), 136-137.
[http://dx.doi.org/10.1038/nchembio.1187] [PMID: 23416387]
[158]
Kubicek, S.; O’Sullivan, R.J.; August, E.M.; Hickey, E.R.; Zhang, Q.; Teodoro, M.L.; Rea, S.; Mechtler, K.; Kowalski, J.A.; Homon, C.A.; Kelly, T.A.; Jenuwein, T. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol. Cell, 2007, 25(3), 473-481.
[http://dx.doi.org/10.1016/j.molcel.2007.01.017] [PMID: 17289593]
[159]
Chang, Y.; Zhang, X.; Horton, J.R.; Upadhyay, A.K.; Spannhoff, A.; Liu, J.; Snyder, J.P.; Bedford, M.T.; Cheng, X. Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294. Nat. Struct. Mol. Biol., 2009, 16(3), 312-317.
[http://dx.doi.org/10.1038/nsmb.1560] [PMID: 19219047]
[160]
Liu, F.; Chen, X.; Allali-Hassani, A.; Quinn, A.M.; Wasney, G.A.; Dong, A.; Barsyte, D.; Kozieradzki, I.; Senisterra, G.; Chau, I.; Siarheyeva, A.; Kireev, D.B.; Jadhav, A.; Herold, J.M.; Frye, S.V.; Arrowsmith, C.H.; Brown, P.J.; Simeonov, A.; Vedadi, M.; Jin, J. Discovery of a 2,4-diamino-7-aminoalkoxyquinazoline as a potent and selective inhibitor of histone lysine methyltransferase G9a. J. Med. Chem., 2009, 52(24), 7950-7953.
[http://dx.doi.org/10.1021/jm901543m] [PMID: 19891491]
[161]
Liu, F.; Barsyte-Lovejoy, D.; Allali-Hassani, A.; He, Y.; Herold, J.M.; Chen, X.; Yates, C.M.; Frye, S.V.; Brown, P.J.; Huang, J.; Vedadi, M.; Arrowsmith, C.H.; Jin, J. Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy-quinazolines. J. Med. Chem., 2011, 54(17), 6139-6150.
[http://dx.doi.org/10.1021/jm200903z] [PMID: 21780790]
[162]
Vedadi, M.; Barsyte-Lovejoy, D.; Liu, F.; Rival-Gervier, S.; Allali-Hassani, A.; Labrie, V.; Wigle, T.J.; DiMaggio, P.A.; Wasney, G.A.; Siarheyeva, A.; Dong, A.; Tempel, W.; Wang, S.C.; Chen, X.; Chau, I.; Mangano, T.J.; Huang, X.; Simpson, C.D.; Pattenden, S.G.; Norris, J.L.; Kireev, D.B.; Tripathy, A.; Edwards, A.; Roth, B.L.; Janzen, W.P.; Garcia, B.A.; Petronis, A.; Ellis, J.; Brown, P.J.; Frye, S.V.; Arrowsmith, C.H.; Jin, J. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat. Chem. Biol., 2011, 7(8), 566-574.
[http://dx.doi.org/10.1038/nchembio.599] [PMID: 21743462]
[163]
Lehnertz, B.; Pabst, C.; Su, L.; Miller, M.; Liu, F.; Yi, L.; Zhang, R.; Krosl, J.; Yung, E.; Kirschner, J.; Rosten, P.; Underhill, T.M.; Jin, J.; Hébert, J.; Sauvageau, G.; Humphries, R.K.; Rossi, F.M. The methyltransferase G9a regulates HoxA9-dependent transcription in AML. Genes Dev., 2014, 28(4), 317-327.
[http://dx.doi.org/10.1101/gad.236794.113] [PMID: 24532712]
[164]
Liu, F.; Barsyte-Lovejoy, D.; Li, F.; Xiong, Y.; Korboukh, V.; Huang, X.P.; Allali-Hassani, A.; Janzen, W.P.; Roth, B.L.; Frye, S.V.; Arrowsmith, C.H.; Brown, P.J.; Vedadi, M.; Jin, J. Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP. J. Med. Chem., 2013, 56(21), 8931-8942.
[http://dx.doi.org/10.1021/jm401480r] [PMID: 24102134]
[165]
Chang, Y.; Ganesh, T.; Horton, J.R.; Spannhoff, A.; Liu, J.; Sun, A.; Zhang, X.; Bedford, M.T.; Shinkai, Y.; Snyder, J.P.; Cheng, X. Adding a lysine mimic in the design of potent inhibitors of histone lysine methyltransferases. J. Mol. Biol., 2010, 400(1), 1-7.
[http://dx.doi.org/10.1016/j.jmb.2010.04.048] [PMID: 20434463]
[166]
Xiong, Y.; Li, F.; Babault, N.; Dong, A.; Zeng, H.; Wu, H.; Chen, X.; Arrowsmith, C.H.; Brown, P.J.; Liu, J.; Vedadi, M.; Jin, J. Discovery of potent and selective inhibitors for G9a-Like Protein (GLP) lysine methyltransferase. J. Med. Chem., 2017, 60(5), 1876-1891.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01645] [PMID: 28135087]
[167]
Yuan, Y.; Wang, Q.; Paulk, J.; Kubicek, S.; Kemp, M.M.; Adams, D.J.; Shamji, A.F.; Wagner, B.K.; Schreiber, S.L. A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma. ACS Chem. Biol., 2012, 7(7), 1152-1157.
[http://dx.doi.org/10.1021/cb300139y] [PMID: 22536950]
[168]
Sweis, R.F.; Pliushchev, M.; Brown, P.J.; Guo, J.; Li, F.; Maag, D.; Petros, A.M.; Soni, N.B.; Tse, C.; Vedadi, M.; Michaelides, M.R.; Chiang, G.G.; Pappano, W.N. Discovery and development of potent and selective inhibitors of histone methyltransferase g9a. ACS Med. Chem. Lett., 2014, 5(2), 205-209.
[http://dx.doi.org/10.1021/ml400496h] [PMID: 24900801]
[169]
Chen, W.L.; Wang, Z.H.; Feng, T.T.; Li, D.D.; Wang, C.H.; Xu, X.L.; Zhang, X.J.; You, Q.D.; Guo, X.K. Discovery, design and synthesis of 6H-anthra[1,9-cd]isoxazol-6-one scaffold as G9a inhibitor through a combination of shape-based virtual screening and structure-based molecular modification. Bioorg. Med. Chem., 2016, 24(22), 6102-6108.
[http://dx.doi.org/10.1016/j.bmc.2016.09.071] [PMID: 27720557]
[170]
Kondengaden, S.M.; Luo, L.; Huang, K.; Zhu, M.; Zang, L.; Bataba, E.; Wang, R.; Luo, C.; Wang, B.; Li, K.K.; Wang, P.G. Discovery of novel small molecule inhibitors of lysine methyltransferase G9a and their mechanism in leukemia cell lines. Eur. J. Med. Chem., 2016, 122, 382-393.
[http://dx.doi.org/10.1016/j.ejmech.2016.06.028] [PMID: 27393948]
[171]
Margueron, R.; Reinberg, D. The Polycomb complex PRC2 and its mark in life. Nature, 2011, 469(7330), 343-349.
[http://dx.doi.org/10.1038/nature09784] [PMID: 21248841]
[172]
Nikoloski, G.; Langemeijer, S.M.C.; Kuiper, R.P.; Knops, R.; Massop, M.; Tönnissen, E.R.L.T.M.; van der Heijden, A.; Scheele, T.N.; Vandenberghe, P.; de Witte, T.; van der Reijden, B.A.; Jansen, J.H. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat. Genet., 2010, 42(8), 665-667.
[http://dx.doi.org/10.1038/ng.620] [PMID: 20601954]
[173]
McCabe, M.T.; Graves, A.P.; Ganji, G.; Diaz, E.; Halsey, W.S.; Jiang, Y.; Smitheman, K.N.; Ott, H.M.; Pappalardi, M.B.; Allen, K.E.; Chen, S.B.; Della Pietra, A., III; Dul, E.; Hughes, A.M.; Gilbert, S.A.; Thrall, S.H.; Tummino, P.J.; Kruger, R.G.; Brandt, M.; Schwartz, B.; Creasy, C.L. Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27). Proc. Natl. Acad. Sci. USA, 2012, 109(8), 2989-2994.
[http://dx.doi.org/10.1073/pnas.1116418109] [PMID: 22323599]
[174]
Margueron, R.; Li, G.; Sarma, K.; Blais, A.; Zavadil, J.; Woodcock, C.L.; Dynlacht, B.D.; Reinberg, D. Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms. Mol. Cell, 2008, 32(4), 503-518.
[http://dx.doi.org/10.1016/j.molcel.2008.11.004] [PMID: 19026781]
[175]
Knutson, S.K.; Wigle, T.J.; Warholic, N.M.; Sneeringer, C.J.; Allain, C.J.; Klaus, C.R.; Sacks, J.D.; Raimondi, A.; Majer, C.R.; Song, J.; Scott, M.P.; Jin, L.; Smith, J.J.; Olhava, E.J.; Chesworth, R.; Moyer, M.P.; Richon, V.M.; Copeland, R.A.; Keilhack, H.; Pollock, R.M.; Kuntz, K.W. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat. Chem. Biol., 2012, 8(11), 890-896.
[http://dx.doi.org/10.1038/nchembio.1084] [PMID: 23023262]
[176]
McCabe, M.T.; Ott, H.M.; Ganji, G.; Korenchuk, S.; Thompson, C.; Van Aller, G.S.; Liu, Y.; Graves, A.P.; Iii, A.D.P.; Diaz, E.; LaFrance, L.V.; Mellinger, M.; Duquenne, C.; Tian, X.; Kruger, R.G.; McHugh, C.F.; Brandt, M.; Miller, W.H.; Dhanak, D.; Verma, S.K.; Tummino, P.J.; Creasy, C.L. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature, 2012, 492(7427), 108-112.
[http://dx.doi.org/10.1038/nature11606] [PMID: 23051747]
[177]
Yap, T.A.; Winter, J.N.; Giulino-Roth, L.; Longley, J.; Lopez, J.; Michot, J.M.; Leonard, J.P.; Ribrag, V.; McCabe, M.T.; Creasy, C.L.; Stern, M.; Pene Dumitrescu, T.; Wang, X.; Frey, S.; Carver, J.; Horner, T.; Oh, C.; Khaled, A.; Dhar, A.; Johnson, P.W.M.; Phase, I. Study of the novel Enhancer of Zeste Homolog 2 (EZH2) Inhibitor GSK2816126 in patients with advanced hematologic and solid tumors. Clin. Cancer Res., 2019, 25(24), 7331-7339.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-4121] [PMID: 31471312]
[178]
Qi, W.; Chan, H.; Teng, L.; Li, L.; Chuai, S.; Zhang, R.; Zeng, J.; Li, M.; Fan, H.; Lin, Y.; Gu, J.; Ardayfio, O.; Zhang, J.H.; Yan, X.; Fang, J.; Mi, Y.; Zhang, M.; Zhou, T.; Feng, G.; Chen, Z.; Li, G.; Yang, T.; Zhao, K.; Liu, X.; Yu, Z.; Lu, C.X.; Atadja, P.; Li, E. Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation. Proc. Natl. Acad. Sci. USA, 2012, 109(52), 21360-21365.
[http://dx.doi.org/10.1073/pnas.1210371110] [PMID: 23236167]
[179]
Konze, K.D.; Ma, A.; Li, F.; Barsyte-Lovejoy, D.; Parton, T.; MacNevin, C.J.; Liu, F.; Gao, C.; Huang, X.P.; Kuznetsova, E.; Rougie, M.; Jiang, A.; Pattenden, S.G.; Norris, J.L.; James, L.I.; Roth, B.L.; Brown, P.J.; Frye, S.V.; Arrowsmith, C.H.; Hahn, K.M.; Wang, G.G.; Vedadi, M.; Jin, J. An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1. ACS Chem. Biol., 2013, 8(6), 1324-1334.
[http://dx.doi.org/10.1021/cb400133j] [PMID: 23614352]
[180]
Knutson, S.K.; Warholic, N.M.; Wigle, T.J.; Klaus, C.R.; Allain, C.J.; Raimondi, A.; Porter Scott, M.; Chesworth, R.; Moyer, M.P.; Copeland, R.A.; Richon, V.M.; Pollock, R.M.; Kuntz, K.W.; Keilhack, H. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc. Natl. Acad. Sci. USA, 2013, 110(19), 7922-7927.
[http://dx.doi.org/10.1073/pnas.1303800110] [PMID: 23620515]
[181]
FDA FDA approves first treatment option specifically for patients with epithelioid sarcoma, a rare soft tissue cancer. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-option-specifically-patients-epithelioid-sarcoma-rare-soft-tissue (Accessed on: 23 January 2020).
[182]
FDA FDA granted accelerated approval to tazemetostat for follicular lymphoma. Available from: https://www.fda.gov/drugs/fda-granted-accelerated-approval-tazemetostat-follicular-lymphoma (Accessed on: 18 June 2020).
[183]
Vaswani, R.G.; Gehling, V.S.; Dakin, L.A.; Cook, A.S.; Nasveschuk, C.G.; Duplessis, M.; Iyer, P.; Balasubramanian, S.; Zhao, F.; Good, A.C.; Campbell, R.; Lee, C.; Cantone, N.; Cummings, R.T.; Normant, E.; Bellon, S.F.; Albrecht, B.K.; Harmange, J.C.; Trojer, P.; Audia, J.E.; Zhang, Y.; Justin, N.; Chen, S.; Wilson, J.R.; Gamblin, S.J. Identification of ( R )- N -((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1- (1-(2,2,2- trifluoroethyl)piperidin-4-yl)ethyl)-1 H -indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitable for Phase I Clinical Trials for B-Cell Lymphomas. J. Med. Chem., 2016, 59(21), 9928-9941.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01315] [PMID: 27739677]
[184]
Campbell, J.E.; Kuntz, K.W.; Knutson, S.K.; Warholic, N.M.; Keilhack, H.; Wigle, T.J.; Raimondi, A.; Klaus, C.R.; Rioux, N.; Yokoi, A.; Kawano, S.; Minoshima, Y.; Choi, H.W.; Porter Scott, M.; Waters, N.J.; Smith, J.J.; Chesworth, R.; Moyer, M.P.; Copeland, R.A. EPZ011989, a potent, orally-available EZH2 inhibitor with robust in vivo activity. ACS Med. Chem. Lett., 2015, 6(5), 491-495.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00037] [PMID: 26005520]
[185]
Song, X.; Gao, T.; Wang, N.; Feng, Q.; You, X.; Ye, T.; Lei, Q.; Zhu, Y.; Xiong, M.; Xia, Y.; Yang, F.; Shi, Y.; Wei, Y.; Zhang, L.; Yu, L. Erratum: Corrigendum: Selective inhibition of EZH2 by ZLD1039 blocks H3K27methylation and leads to potent anti-tumor activity in breast cancer. Sci. Rep., 2016, 6(1), 24893.
[http://dx.doi.org/10.1038/srep24893] [PMID: 27128979]
[186]
Gao, T.; Zhang, L.; Zhu, Y.; Song, X.; Feng, Q.; Lei, Q.; Shi, S.; Deng, H.; Xiong, M.; You, X.; Zuo, W.; Liu, L.; Peng, C.; Wang, N.; Ye, T.; Xia, Y.; Yu, L. ZLD1122, a novel EZH2 and EZH1 small molecular inhibitor, blocks H3K27 methylation and diffuse large B cell lymphoma cell growth. RSC Advances, 2016, 6(34), 28512-28521.
[http://dx.doi.org/10.1039/C6RA00618C]
[187]
Garapaty-Rao, S.; Nasveschuk, C.; Gagnon, A.; Chan, E.Y.; Sandy, P.; Busby, J.; Balasubramanian, S.; Campbell, R.; Zhao, F.; Bergeron, L.; Audia, J.E.; Albrecht, B.K.; Harmange, J.C.; Cummings, R.; Trojer, P. Identification of EZH2 and EZH1 small molecule inhibitors with selective impact on diffuse large B cell lymphoma cell growth. Chem. Biol., 2013, 20(11), 1329-1339.
[http://dx.doi.org/10.1016/j.chembiol.2013.09.013] [PMID: 24183969]
[188]
Kung, P.P.; Rui, E.; Bergqvist, S.; Bingham, P.; Braganza, J.; Collins, M.; Cui, M.; Diehl, W.; Dinh, D.; Fan, C.; Fantin, V.R.; Gukasyan, H.J.; Hu, W.; Huang, B.; Kephart, S.; Krivacic, C.; Kumpf, R.A.; Li, G.; Maegley, K.A.; McAlpine, I.; Nguyen, L.; Ninkovic, S.; Ornelas, M.; Ryskin, M.; Scales, S.; Sutton, S.; Tatlock, J.; Verhelle, D.; Wang, F.; Wells, P.; Wythes, M.; Yamazaki, S.; Yip, B.; Yu, X.; Zehnder, L.; Zhang, W.G.; Rollins, R.A.; Edwards, M. Design and synthesis of pyridone-containing 3,4-dihydroisoquinoline-1(2 H )-ones as a Novel Class of Enhancer of Zeste Homolog 2 (EZH2) Inhibitors. J. Med. Chem., 2016, 59(18), 8306-8325.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00515] [PMID: 27512831]
[189]
Kikuchi, J.; Takashina, T.; Kinoshita, I.; Kikuchi, E.; Shimizu, Y.; Sakakibara-Konishi, J.; Oizumi, S.; Marquez, V.E.; Nishimura, M.; Dosaka-Akita, H. Epigenetic therapy with 3-deazaneplanocin A, an inhibitor of the histone methyltransferase EZH2, inhibits growth of non-small cell lung cancer cells. Lung Cancer, 2012, 78(2), 138-143.
[http://dx.doi.org/10.1016/j.lungcan.2012.08.003] [PMID: 22925699]
[190]
Bromberg, K.D.; Mitchell, T.R.H.; Upadhyay, A.K.; Jakob, C.G.; Jhala, M.A.; Comess, K.M.; Lasko, L.M.; Li, C.; Tuzon, C.T.; Dai, Y.; Li, F.; Eram, M.S.; Nuber, A.; Soni, N.B.; Manaves, V.; Algire, M.A.; Sweis, R.F.; Torrent, M.; Schotta, G.; Sun, C.; Michaelides, M.R.; Shoemaker, A.R.; Arrowsmith, C.H.; Brown, P.J.; Santhakumar, V.; Martin, A.; Rice, J.C.; Chiang, G.G.; Vedadi, M.; Barsyte-Lovejoy, D.; Pappano, W.N. The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity. Nat. Chem. Biol., 2017, 13(3), 317-324.
[http://dx.doi.org/10.1038/nchembio.2282] [PMID: 28114273]
[191]
Sawada, K.; Yang, Z.; Horton, J.R.; Collins, R.E.; Zhang, X.; Cheng, X. Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase. J. Biol. Chem., 2004, 279(41), 43296-43306.
[http://dx.doi.org/10.1074/jbc.M405902200] [PMID: 15292170]
[192]
Min, J.; Feng, Q.; Li, Z.; Zhang, Y.; Xu, R.M. Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase. Cell, 2003, 112(5), 711-723.
[http://dx.doi.org/10.1016/S0092-8674(03)00114-4] [PMID: 12628190]
[193]
Nguyen, A.T.; Zhang, Y. The diverse functions of Dot1 and H3K79 methylation. Genes Dev., 2011, 25(13), 1345-1358.
[http://dx.doi.org/10.1101/gad.2057811] [PMID: 21724828]
[194]
Nguyen, A.T.; He, J.; Taranova, O.; Zhang, Y. Essential role of DOT1L in maintaining normal adult hematopoiesis. Cell Res., 2011, 21(9), 1370-1373.
[http://dx.doi.org/10.1038/cr.2011.115] [PMID: 21769133]
[195]
Nguyen, A.T.; Xiao, B.; Neppl, R.L.; Kallin, E.M.; Li, J.; Chen, T.; Wang, D.Z.; Xiao, X.; Zhang, Y. DOT1L regulates dystrophin expression and is critical for cardiac function. Genes Dev., 2011, 25(3), 263-274.
[http://dx.doi.org/10.1101/gad.2018511] [PMID: 21289070]
[196]
Chang, M.J.; Wu, H.; Achille, N.J.; Reisenauer, M.R.; Chou, C.W.; Zeleznik-Le, N.J.; Hemenway, C.S.; Zhang, W. Histone H3 lysine 79 methyltransferase Dot1 is required for immortalization by MLL oncogenes. Cancer Res., 2010, 70(24), 10234-10242.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-3294] [PMID: 21159644]
[197]
Daigle, S.R.; Olhava, E.J.; Therkelsen, C.A.; Majer, C.R.; Sneeringer, C.J.; Song, J.; Johnston, L.D.; Scott, M.P.; Smith, J.J.; Xiao, Y.; Jin, L.; Kuntz, K.W.; Chesworth, R.; Moyer, M.P.; Bernt, K.M.; Tseng, J.C.; Kung, A.L.; Armstrong, S.A.; Copeland, R.A.; Richon, V.M.; Pollock, R.M. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell, 2011, 20(1), 53-65.
[http://dx.doi.org/10.1016/j.ccr.2011.06.009] [PMID: 21741596]
[198]
Yu, W.; Chory, E.J.; Wernimont, A.K.; Tempel, W.; Scopton, A.; Federation, A.; Marineau, J.J.; Qi, J.; Barsyte-Lovejoy, D.; Yi, J.; Marcellus, R.; Iacob, R.E.; Engen, J.R.; Griffin, C.; Aman, A.; Wienholds, E.; Li, F.; Pineda, J.; Estiu, G.; Shatseva, T.; Hajian, T.; Al-awar, R.; Dick, J.E.; Vedadi, M.; Brown, P.J.; Arrowsmith, C.H.; Bradner, J.E.; Schapira, M. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat. Commun., 2012, 3(1), 1288.
[http://dx.doi.org/10.1038/ncomms2304] [PMID: 23250418]
[199]
Daigle, S.R.; Olhava, E.J.; Therkelsen, C.A.; Basavapathruni, A.; Jin, L.; Boriack-Sjodin, P.A.; Allain, C.J.; Klaus, C.R.; Raimondi, A.; Scott, M.P.; Waters, N.J.; Chesworth, R.; Moyer, M.P.; Copeland, R.A.; Richon, V.M.; Pollock, R.M. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood, 2013, 122(6), 1017-1025.
[http://dx.doi.org/10.1182/blood-2013-04-497644] [PMID: 23801631]
[200]
Waters, N.J.; Smith, S.A.; Olhava, E.J.; Duncan, K.W.; Burton, R.D.; O’Neill, J.; Rodrigue, M.E.; Pollock, R.M.; Moyer, M.P.; Chesworth, R. Metabolism and disposition of the DOT1L inhibitor, pinometostat (EPZ-5676), in rat, dog and human. Cancer Chemother. Pharmacol., 2016, 77(1), 43-62.
[http://dx.doi.org/10.1007/s00280-015-2929-y] [PMID: 26645404]
[201]
Stein, E.M.; Garcia-Manero, G.; Rizzieri, D.A.; Tibes, R.; Berdeja, J.G.; Savona, M.R.; Jongen-Lavrenic, M.; Altman, J.K.; Thomson, B.; Blakemore, S.J.; Daigle, S.R.; Waters, N.J.; Suttle, A.B.; Clawson, A.; Pollock, R.; Krivtsov, A.; Armstrong, S.A.; DiMartino, J.; Hedrick, E.; Löwenberg, B.; Tallman, M.S. The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia. Blood, 2018, 131(24), 2661-2669.
[http://dx.doi.org/10.1182/blood-2017-12-818948] [PMID: 29724899]
[202]
Yao, Y.; Chen, P.; Diao, J.; Cheng, G.; Deng, L.; Anglin, J.L.; Prasad, B.V.V.; Song, Y. Selective inhibitors of histone methyltransferase DOT1L: Design, synthesis, and crystallographic studies. J. Am. Chem. Soc., 2011, 133(42), 16746-16749.
[http://dx.doi.org/10.1021/ja206312b] [PMID: 21936531]
[203]
Yu, W.; Smil, D.; Li, F.; Tempel, W.; Fedorov, O.; Nguyen, K.T.; Bolshan, Y.; Al-Awar, R.; Knapp, S.; Arrowsmith, C.H.; Vedadi, M.; Brown, P.J.; Schapira, M. Bromo-deaza-SAH: A potent and selective DOT1L inhibitor. Bioorg. Med. Chem., 2013, 21(7), 1787-1794.
[http://dx.doi.org/10.1016/j.bmc.2013.01.049] [PMID: 23433670]
[204]
Spurr, S.S.; Bayle, E.D.; Yu, W.; Li, F.; Tempel, W.; Vedadi, M.; Schapira, M.; Fish, P.V. New small molecule inhibitors of histone methyl transferase DOT1L with a nitrile as a non-traditional replacement for heavy halogen atoms. Bioorg. Med. Chem. Lett., 2016, 26(18), 4518-4522.
[http://dx.doi.org/10.1016/j.bmcl.2016.07.041] [PMID: 27485386]
[205]
Anglin, J.L.; Deng, L.; Yao, Y.; Cai, G.; Liu, Z.; Jiang, H.; Cheng, G.; Chen, P.; Dong, S.; Song, Y. Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L. J. Med. Chem., 2012, 55(18), 8066-8074.
[http://dx.doi.org/10.1021/jm300917h] [PMID: 22924785]
[206]
Chen, S.; Li, L.; Chen, Y.; Hu, J.; Liu, J.; Liu, Y.C.; Liu, R.; Zhang, Y.; Meng, F.; Zhu, K.; Lu, J.; Zheng, M.; Chen, K.; Zhang, J.; Jiang, H.; Yao, Z.; Luo, C. Identification of Novel Disruptor of Telomeric Silencing 1-like (DOT1L) Inhibitors through Structure-Based Virtual Screening and Biological Assays. J. Chem. Inf. Model., 2016, 56(3), 527-534.
[http://dx.doi.org/10.1021/acs.jcim.5b00738] [PMID: 26914852]
[207]
Luo, M.; Wang, H.; Zou, Y.; Zhang, S.; Xiao, J.; Jiang, G.; Zhang, Y.; Lai, Y. Identification of phenoxyacetamide derivatives as novel DOT1L inhibitors via docking screening and molecular dynamics simulation. J. Mol. Graph. Model., 2016, 68, 128-139.
[http://dx.doi.org/10.1016/j.jmgm.2016.06.011] [PMID: 27434826]
[208]
Chen, C.; Zhu, H.; Stauffer, F.; Caravatti, G.; Vollmer, S.; Machauer, R.; Holzer, P.; Möbitz, H.; Scheufler, C.; Klumpp, M.; Tiedt, R.; Beyer, K.S.; Calkins, K.; Guthy, D.; Kiffe, M.; Zhang, J.; Gaul, C. Discovery of novel Dot1L inhibitors through a structure-based fragmentation approach. ACS Med. Chem. Lett., 2016, 7(8), 735-740.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00167] [PMID: 27563395]
[209]
Scheufler, C.; Möbitz, H.; Gaul, C.; Ragot, C.; Be, C.; Fernández, C.; Beyer, K.S.; Tiedt, R.; Stauffer, F. Optimization of a fragment-based screening hit toward potent DOT1L inhibitors interacting in an induced binding pocket. ACS Med. Chem. Lett., 2016, 7(8), 730-734.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00168] [PMID: 27563394]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy