Strategies for the Discovery of Target-Specific or Isoform-Selective Modulators

Journal of Medicinal Chemistry

Volumn 58, Issue 19, 2015, Pages 7611-7633

  Zhan, Peng ^a   Itoh, Yukihiro ^b   Suzuki, Takayoshi ^b,c   Liu, Xinyong ^a  

^a SHANDONG UNIVERSITY   (China)

^b KYOTO PREFECTURAL UNIVERSITY OF MEDICINE   (Japan)

^c JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ISOFORM SELECTIVE INHIBITOR; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; ENZYME INHIBITOR; ISOENZYME; MOLECULAR LIBRARY;

ANIMAL EXPERIMENT; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; COMBINATORIAL CHEMISTRY; CONTROLLED STUDY; DERIVATIZATION; DRUG DESIGN; DRUG MECHANISM; DRUG SCREENING; DRUG STRUCTURE; HUMAN; HUMAN CELL; IN VITRO STUDY; MOLECULE; NONHUMAN; RAT; CHEMISTRY; MOLECULAR LIBRARY; MOLECULARLY TARGETED THERAPY; PHARMACOLOGY; PRECLINICAL STUDY; PROCEDURES; STRUCTURE ACTIVITY RELATION;

COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; ISOENZYMES; MOLECULAR TARGETED THERAPY; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84943779677     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b00229     Document Type: Article

References (92)

1. Morphy, R. Selectively nonselective kinase inhibition: striking the right balance J. Med. Chem. 2010, 53, 1413-1437
2. Jeong, Y.; Kwon, D.; Hong, S. Selective and potent small-molecule inhibitors of PI3Ks Future Med. Chem. 2014, 6, 737-756
3. Hojjat-Farsangi, M. Small-molecule inhibitors of the receptor tyrosine kinases: promising tools for targeted cancer therapies Int. J. Mol. Sci. 2014, 15, 13768-13801
4. Dymock, B. W.; Yang, E. G.; Chu-Farseeva, Y.; Yao, L. Selective JAK inhibitors Future Med. Chem. 2014, 6, 1439-1471
5. Falkenberg, K. J.; Johnstone, R. W. Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders Nature Rev. Drug. Discovery 2014, 13, 673-691
6. Suzuki, T. Explorative study on isoform-selective histone deacetylase inhibitors Chem. Pharm. Bull. 2009, 57, 897-906
7. Alterio, V.; Di Fiore, A.; DAmbrosio, K.; Supuran, C. T.; De Simone, G. Multiple binding modes of inhibitors to carbonic anhydrases: how to design specific drugs targeting 15 different isoforms? Chem. Rev. 2012, 112, 4421-4468
8. Bhat, R.; Tummalapalli, S. R.; Rotella, D. P. Progress in the discovery and development of heat shock protein 90 (Hsp90) Inhibitors J. Med. Chem. 2014, 57, 8718-8728
9. Erdal, E. P.; Litzinger, E. A.; Seo, J.; Zhu, Y.; Ji, H.; Silverman, R. B. Selective neuronal nitric oxide synthase inhibitors Curr. Top Med. Chem. 2005, 5, 603-624
10. Zhan, P.; Song, Y.; Itoh, Y.; Suzuki, T.; Liu, X. Recent advances in the structure-based rational design of TNKSIs Mol. Biosyst. 2014, 10, 2783-2799
11. Thinnes, C. C.; England, K. S.; Kawamura, A.; Chowdhury, R.; Schofield, C. J.; Hopkinson, R. J. Targeting histone lysine demethylases-progress, challenges, and the future Biochim. Biophys. Acta 2014, 1839, 1416-1432
12. Højfeldt, J. W.; Agger, K.; Helin, K. Histone lysine demethylases as targets for anticancer therapy Nature Rev. Drug Discovery 2013, 12, 917-930
13. Huggins, D. J.; Sherman, W.; Tidor, B. Rational approaches to improving selectivity in drug design J. Med. Chem. 2012, 55, 1424-1444
14. Ji, H.; Stanton, B. Z.; Igarashi, J.; Li, H.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Minimal pharmacophoric elements and fragment hopping, an approach directed at molecular diversity and isozyme selectivity. Design of selective neuronal nitric oxide synthase inhibitors J. Am. Chem. Soc. 2008, 130, 3900-3914
15. Ji, H.; Li, H.; Martásek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. Discovery of highly potent and selective inhibitors of neuronal nitric oxide synthase by fragment hopping J. Med. Chem. 2009, 52, 779-797
16. Suzuki, T.; Miyata, N. Lysine demethylases inhibitors J. Med. Chem. 2011, 54, 8236-8250
17. Khan, M. N.; Suzuki, T.; Miyata, N. An overview of phenylcyclopropylamine derivatives: biochemical and biological significance and recent developments Med. Res. Rev. 2013, 33, 873-910
18. Culhane, J. C.; Szewczuk, L. M.; Liu, X.; Da, G.; Marmorstein, R.; Cole, P. A. A mechanism-based inactivator for histone demethylase LSD1 J. Am. Chem. Soc. 2006, 128, 4536-4537
19. Szewczuk, L. M.; Culhane, J. C.; Yang, M.; Majumdar, A.; Yu, H.; Cole, P. A. Mechanistic analysis of a suicide inactivator of histone demethylase LSD1 Biochemistry 2007, 46, 6892-6902
20. Ueda, R.; Suzuki, T.; Mino, K.; Tsumoto, H.; Nakagawa, H.; Hasegawa, M.; Sasaki, R.; Mizukami, T.; Miyata, N. Identification of cell-active lysine specific demethylase 1-selective inhibitors J. Am. Chem. Soc. 2009, 131, 17536-17537
21. Ogasawara, D.; Itoh, Y.; Tsumoto, H.; Kakizawa, T.; Mino, K.; Fukuhara, K.; Nakagawa, H.; Hasegawa, M.; Sasaki, R.; Mizukami, T.; Miyata, N.; Suzuki, T. Lysine-specific demethylase 1-selective inactivators: protein-targeted drug delivery mechanism Angew. Chem., Int. Ed. Engl. 2013, 52, 8620-8624
22. Lewis, W. G.; Green, L. G.; Grynszpan, F.; Radić, Z.; Carlier, P. R.; Taylor, P.; Finn, M. G.; Sharpless, K. B. Click chemistry in situ: acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks Angew. Chem., Int. Ed. Engl. 2002, 41, 1053-1057
23. Manetsch, R.; Krasiński, A.; Radić, Z.; Raushel, J.; Taylor, P.; Sharpless, K. B.; Kolb, H. C. In situ click chemistry: enzyme inhibitors made to their own specifications J. Am. Chem. Soc. 2004, 126, 12809-12818
24. Nasr, G.; Petit, E.; Vullo, D.; Winum, J. Y.; Supuran, C. T.; Barboiu, M. Carbonic anhydrase-encoded dynamic constitutional libraries: toward the discovery of isozyme-specific inhibitors J. Med. Chem. 2009, 52, 4853-4859
25. Yamauchi, J. G.; Gomez, K.; Grimster, N.; Dufouil, M.; Nemecz, A.; Fotsing, J. R.; Ho, K. Y.; Talley, T. T.; Sharpless, K. B.; Fokin, V. V.; Taylor, P. Synthesis of selective agonists for the α7 nicotinic acetylcholine receptor with in situ click-chemistry on acetylcholine-binding protein templates Mol. Pharmacol. 2012, 82, 687-699
26. Suzuki, T.; Ota, Y.; Kasuya, Y.; Mutsuga, M.; Kawamura, Y.; Tsumoto, H.; Nakagawa, H.; Finn, M. G.; Miyata, N. An unexpected example of protein-templated click chemistry Angew. Chem., Int. Ed. Engl. 2010, 49, 6817-6820
27. Danishuddin, M.; Khan, A. U. Structure based virtual screening to discover putative drug candidates: necessary considerations and successful case studies Methods 2015, 71C, 135-145
28. Braga, R. C.; Alves, V. M.; Silva, A. C.; Nascimento, M. N.; Silva, F. C.; Liao, L. M.; Andrade, C. H. Virtual screening strategies in medicinal chemistry: the state of the art and current challenges Curr. Top Med. Chem. 2014, 14, 1899-1912
29. Lionta, E.; Spyrou, G.; Vassilatis, D. K.; Cournia, Z. Structure-based virtual screening for drug discovery: principles, applications and recent advances Curr. Top Med. Chem. 2014, 14, 1923-1938
30. Brožič, P.; Turk, S.; Adeniji, A. O.; Konc, J.; Janežič, D.; Penning, T. M.; Lanišnik Rižner, T.; Gobec, S. Selective inhibitors of aldo-keto reductases AKR1C1 and AKR1C3 discovered by virtual screening of a fragment library J. Med. Chem. 2012, 55, 7417-7424
31. Brus, B.; Košak, U.; Turk, S.; Pišlar, A.; Coquelle, N.; Kos, J.; Stojan, J.; Colletier, J. P.; Gobec, S. Discovery, biological evaluation, and crystal structure of a novel nanomolar selective butyrylcholinesterase inhibitor J. Med. Chem. 2014, 57, 8167-8179
32. Chen, Y. Beware of docking! Trends Pharmacol. Sci. 2015, 36, 78-95
33. Wang, T.; Wu, M. B.; Chen, Z. J.; Chen, H.; Lin, J. P.; Yang, L. R. Fragment-based drug discovery and molecular docking in drug design Curr. Pharm. Biotechnol. 2015, 16, 11-25
34. Suzuki, T.; Kouketsu, A.; Itoh, Y.; Hisakawa, S.; Maeda, S.; Yoshida, M.; Nakagawa, H.; Miyata, N. Highly potent and selective histone deacetylase 6 inhibitors designed based on a small-molecular substrate J. Med. Chem. 2006, 49, 4809-4812
35. Itoh, Y.; Suzuki, T.; Kouketsu, A.; Suzuki, N.; Maeda, S.; Yoshida, M.; Nakagawa, H.; Miyata, N. Design, synthesis, structure-selectivity relationship, and effect on human cancer cells of a novel series of histone deacetylase 6-selective inhibitors J. Med. Chem. 2007, 50, 5425-5438
36. Asaba, T.; Suzuki, T.; Ueda, R.; Tsumoto, H.; Nakagawa, H.; Miyata, N. Inhibition of human sirtuins by in situ generation of an acetylated lysine-ADP-ribose conjugate J. Am. Chem. Soc. 2009, 131, 6989-6996
37. Cui, H.; Kamal, Z.; Ai, T.; Xu, Y.; More, S. S.; Wilson, D. J.; Chen, L. Discovery of potent and selective sirtuin 2 (SIRT2) inhibitors using a fragment-based approach J. Med. Chem. 2014, 57, 8340-8357
38. Pilka, E. S.; James, T.; Lisztwan, J. H. Structural definitions of Jumonji family demethylase selectivity Drug Discovery Today. 2014, 20, 743-749 10.1016/j.drudis.2014.12.013
39. Luo, X.; Liu, Y.; Kubicek, S.; Myllyharju, J.; Tumber, A.; Ng, S.; Che, K. H.; Podoll, J.; Heightman, T. D.; Oppermann, U.; Schreiber, S. L.; Wang, X. A selective inhibitor and probe of the cellular functions of Jumonji C domain-containing histone demethylases J. Am. Chem. Soc. 2011, 133, 9451-9456
40. Baguley, T. D.; Xu, H. C.; Chatterjee, M.; Nairn, A. C.; Lombroso, P. J.; Ellman, J. A. Substrate-based fragment identification for the development of selective, nonpeptidic inhibitors of striatal-enriched protein tyrosine phosphatase J. Med. Chem. 2013, 56, 7636-7650
41. Baguley, T. D.; Xu, H. C.; Chatterjee, M.; Nairn, A. C.; Lombroso, P. J.; Ellman, J. A. Correction to substrate-based fragment identification for the development of selective, nonpeptidic inhibitors of striatal-enriched protein tyrosine phosphatase J. Med. Chem. 2014, 57, 10564-10564
42. Lavogina, D.; Enkvist, E.; Uri, A. Bisubstrate inhibitors of protein kinases: from principle to practical applications ChemMedChem 2010, 5, 23-34
43. Lamba, V.; Ghosh, I. New directions in targeting protein kinases: focusing upon true allosteric and bivalent inhibitors Curr. Pharm. Des. 2012, 18, 2936-2945
44. Ekambaram, R.; Enkvist, E.; Vaasa, A.; Kasari, M.; Raidaru, G.; Knapp, S.; Uri, A. Selective bisubstrate inhibitors with sub-nanomolar affinity for protein kinase Pim-1 ChemMedChem 2013, 8, 909-913
45. van Wandelen, L. T.; van Ameijde, J.; Ismail-Ali, A. F.; van Ufford, H. C.; Vijftigschild, L. A.; Beekman, J. M.; Martin, N. I.; Ruijtenbeek, R.; Liskamp, R. M. Cell-penetrating bisubstrate-based protein kinase C inhibitors ACS Chem. Biol. 2013, 8, 1479-1487
46. Poot, A. J.; van Ameijde, J.; Slijper, M.; van den Berg, A.; Hilhorst, R.; Ruijtenbeek, R.; Rijkers, D. T.; Liskamp, R. M. Development of selective bisubstrate-based inhibitors against protein kinase C (PKC) isozymes by using dynamic peptide microarrays ChemBioChem 2009, 10, 2042-2051
47. van Wandelen, L. T.; van Ameijde, J.; Mady, A. S.; Wammes, A. E.; Bode, A.; Poot, A. J.; Ruijtenbeek, R.; Liskamp, R. M. Directed modulation of protein kinase C isozyme selectivity with bisubstrate-based inhibitors ChemMedChem 2012, 7, 2113-2121
48. Song, Y.; Zhan, P.; Li, X.; Rai, D.; De Clercq, E.; Liu, X. Multivalent agents: a novel concept and preliminary practice in anti-HIV drug discovery Curr. Med. Chem. 2013, 20, 815-832
49. Zhu, J.; Yang, Q.; Dai, D.; Huang, Q. X-ray crystal structure of phosphodiesterase 2 in complex with a highly selective, nanomolar inhibitor reveals a binding-induced pocket important for selectivity J. Am. Chem. Soc. 2013, 135, 11708-11711
50. Fabre, B.; Ramos, A.; de Pascual-Teresa, B. Targeting matrix metalloproteinases: exploring the dynamics of the S1′ pocket in the design of selective, small molecule inhibitors J. Med. Chem. 2014, 57, 10205-10219
51. Nara, H.; Sato, K.; Naito, T.; Mototani, H.; Oki, H.; Yamamoto, Y.; Kuno, H.; Santou, T.; Kanzaki, N.; Terauchi, J.; Uchikawa, O.; Kori, M. Discovery of novel, highly potent and selective quinazoline-2-carboxamide-based matrix metalloproteinase (MMP)-13 inhibitors without zinc binding group using structure-based design approach J. Med. Chem. 2014, 57, 8886-8902
52. Nara, H.; Sato, K.; Naito, T.; Mototani, H.; Oki, H.; Yamamoto, Y.; Kuno, H.; Santou, T.; Kanzaki, N.; Terauchi, J.; Uchikawa, O.; Kori, M. Thieno[2,3-d]pyrimidine-2-carboxamides bearing a carboxybenzene group at 5-position: highly potent, selective, and orally available MMP-13 inhibitors interacting with the S1 binding site Bioorg. Med. Chem. 2014, 22, 5487-5505
53. Schonbrunn, E.; Betzi, S.; Alam, R.; Martin, M. P.; Becker, A.; Han, H.; Francis, R.; Chakrasali, R.; Jakkaraj, S.; Kazi, A.; Sebti, S. M.; Cubitt, C. L.; Gebhard, A. W.; Hazlehurst, L. A.; Tash, J. S.; Georg, G. I. Development of highly potent and selective diaminothiazole inhibitors of cyclin-dependent kinases J. Med. Chem. 2013, 56, 3768-3782
54. Meng, F.; Hou, J.; Shao, Y. X.; Wu, P. Y.; Huang, M.; Zhu, X.; Cai, Y.; Li, Z.; Xu, J.; Liu, P.; Luo, H. B.; Wan, Y.; Ke, H. Structure-based discovery of highly selective phosphodiesterase-9A inhibitors and implications for inhibitor design J. Med. Chem. 2012, 55, 8549-8558
55. Folkes, A. J.; Ahmadi, K.; Alderton, W. K.; Alix, S.; Baker, S. J.; Box, G.; Chuckowree, I. S.; Clarke, P. A.; Depledge, P.; Eccles, S. A.; Friedman, L. S.; Hayes, A.; Hancox, T. C.; Kugendradas, A.; Lensun, L.; Moore, P.; Olivero, A. G.; Pang, J.; Patel, S.; Pergl-Wilson, G. H.; Raynaud, F. I.; Robson, A.; Saghir, N.; Salphati, L.; Sohal, S.; Ultsch, M. H.; Valenti, M.; Wallweber, H. J.; Wan, N. C.; Wiesmann, C.; Workman, P.; Zhyvoloup, A.; Zvelebil, M. J.; Shuttleworth, S. J. The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer J. Med. Chem. 2008, 51, 5522-5532
56. Nacht, M.; Qiao, L.; Sheets, M. P.; Martin, T., St; Labenski, M.; Mazdiyasni, H.; Karp, R.; Zhu, Z.; Chaturvedi, P.; Bhavsar, D.; Niu, D.; Westlin, W.; Petter, R. C.; Medikonda, A. P.; Singh, J. Discovery of a potent and isoform-selective targeted covalent inhibitor of the lipid kinase PI3Kα J. Med. Chem. 2013, 56, 712-721
57. Schröder, J.; Klinger, A.; Oellien, F.; Marhöfer, R. J.; Duszenko, M.; Selzer, P. M. Docking-based virtual screening of covalently binding ligands: an orthogonal lead discovery approach J. Med. Chem. 2013, 56, 1478-1490
58. Pinson, J. A.; Zheng, Z.; Miller, M. S.; Chalmers, D. K.; Jennings, I. G.; Thompson, P. E. l -Aminoacyl-triazine derivatives are isoform-selective PI3Kβ inhibitors that target non-conserved Asp862 of PI3Kβ ACS Med. Chem. Lett. 2013, 4, 206-210
59. Leahy, J. W.; Buhr, C. A.; Johnson, H. W.; Kim, B. G.; Baik, T.; Cannoy, J.; Forsyth, T. P.; Jeong, J. W.; Lee, M. S.; Ma, S.; Noson, K.; Wang, L.; Williams, M.; Nuss, J. M.; Brooks, E.; Foster, P.; Goon, L.; Heald, N.; Holst, C.; Jaeger, C.; Lam, S.; Lougheed, J.; Nguyen, L.; Plonowski, A.; Song, J.; Stout, T.; Wu, X.; Yakes, M. F.; Yu, P.; Zhang, W.; Lamb, P.; Raeber, O. Discovery of a novel series of potent and orally bioavailable phosphoinositide 3-kinase γ inhibitors J. Med. Chem. 2012, 55, 5467-5482
60. Bago, R.; Malik, N.; Munson, M. J.; Prescott, A. R.; Davies, P.; Sommer, E.; Shpiro, N.; Ward, R.; Cross, D.; Ganley, I. G.; Alessi, D. R. Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase Biochem. J. 2014, 463, 413-427
61. Ronan, B.; Flamand, O.; Vescovi, L.; Dureuil, C.; Durand, L.; Fassy, F.; Bachelot, M. F.; Lamberton, A.; Mathieu, M.; Bertrand, T.; Marquette, J. P.; El-Ahmad, Y.; Filoche-Romme, B.; Schio, L.; Garcia-Echeverria, C.; Goulaouic, H.; Pasquier, B. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy Nature Chem. Biol. 2014, 10, 1013-1019
62. Pasquier, B.; El-Ahmad, Y.; Filoche-Rommé, B.; Dureuil, C.; Fassy, F.; Abecassis, P. Y.; Mathieu, M.; Bertrand, T.; Benard, T.; Barrière, C.; El Batti, S.; Letallec, J. P.; Sonnefraud, V.; Brollo, M.; Delbarre, L.; Loyau, V.; Pilorge, F.; Bertin, L.; Richepin, P.; Arigon, J.; Labrosse, J. R.; Clément, J.; Durand, F.; Combet, R.; Perraut, P.; Leroy, V.; Gay, F.; Lefrançois, D.; Bretin, F.; Marquette, J. P.; Michot, N.; Caron, A.; Castell, C.; Schio, L.; McCort, G.; Goulaouic, H.; Garcia-Echeverria, C.; Ronan, B. Discovery of (2S)-8-[(3R)-3-methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: a novel potent and selective inhibitor of Vps34 for the treatment of solid tumors J. Med. Chem. 2015, 58, 376-400
63. Duerfeldt, A. S.; Peterson, L. B.; Maynard, J. C.; Ng, C. L.; Eletto, D.; Ostrovsky, O.; Shinogle, H. E.; Moore, D. S.; Argon, Y.; Nicchitta, C. V.; Blagg, B. S. Development of a Grp94 inhibitor J. Am. Chem. Soc. 2012, 134, 9796-9804
64. Lucas, M. C.; Goldstein, D. M.; Hermann, J. C.; Kuglstatter, A.; Liu, W.; Luk, K. C.; Padilla, F.; Slade, M.; Villaseñor, A. G.; Wanner, J.; Xie, W.; Zhang, X.; Liao, C. Rational design of highly selective spleen tyrosine kinase inhibitors J. Med. Chem. 2012, 55, 10414-10423
65. Liang, J.; van Abbema, A.; Balazs, M.; Barrett, K.; Berezhkovsky, L.; Blair, W.; Chang, C.; Delarosa, D.; DeVoss, J.; Driscoll, J.; Eigenbrot, C.; Ghilardi, N.; Gibbons, P.; Halladay, J.; Johnson, A.; Kohli, P. B.; Lai, Y.; Liu, Y.; Lyssikatos, J.; Mantik, P.; Menghrajani, K.; Murray, J.; Peng, I.; Sambrone, A.; Shia, S.; Shin, Y.; Smith, J.; Sohn, S.; Tsui, V.; Ultsch, M.; Wu, L. C.; Xiao, Y.; Yang, W.; Young, J.; Zhang, B.; Zhu, B. Y.; Magnuson, S. Lead optimization of a 4-aminopyridine benzamide scaffold to identify potent, selective, and orally bioavailable TYK2 inhibitors J. Med. Chem. 2013, 56, 4521-4536
66. Zak, M.; Hurley, C. A.; Ward, S. I.; Bergeron, P.; Barrett, K.; Balazs, M.; Blair, W. S.; Bull, R.; Chakravarty, P.; Chang, C.; Crackett, P.; Deshmukh, G.; DeVoss, J.; Dragovich, P. S.; Eigenbrot, C.; Ellwood, C.; Gaines, S.; Ghilardi, N.; Gibbons, P.; Gradl, S.; Gribling, P.; Hamman, C.; Harstad, E.; Hewitt, P.; Johnson, A.; Johnson, T.; Kenny, J. R.; Koehler, M. F.; Bir Kohli, P.; Labadie, S.; Lee, W. P.; Liao, J.; Liimatta, M.; Mendonca, R.; Narukulla, R.; Pulk, R.; Reeve, A.; Savage, S.; Shia, S.; Steffek, M.; Ubhayakar, S.; van Abbema, A.; Aliagas, I.; Avitabile-Woo, B.; Xiao, Y.; Yang, J.; Kulagowski, J. J. Identification of C-2 hydroxyethyl imidazopyrrolopyridines as potent JAK1 inhibitors with favorable physicochemical properties and high selectivity over JAK2 J. Med. Chem. 2013, 56, 4764-4785
67. Jaime-Figueroa, S.; De Vicente, J.; Hermann, J.; Jahangir, A.; Jin, S.; Kuglstatter, A.; Lynch, S. M.; Menke, J.; Niu, L.; Patel, V.; Shao, A.; Soth, M.; Vu, M. D.; Yee, C. Discovery of a series of novel 5H-pyrrolo[2,3-b]pyrazine-2-phenyl ethers, as potent JAK3 kinase inhibitors Bioorg. Med. Chem, Lett. 2013, 23, 2522-2526
68. Butler, K. V.; Kalin, J.; Brochier, C.; Vistoli, G.; Langley, B.; Kozikowski, A. P. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A J. Am. Chem. Soc. 2010, 132, 10842-10846
69. Hamada, S.; Suzuki, T.; Mino, K.; Koseki, K.; Oehme, F.; Flamme, I.; Ozasa, H.; Itoh, Y.; Ogasawara, D.; Komaarashi, H.; Kato, A.; Tsumoto, H.; Nakagawa, H.; Hasegawa, M.; Sasaki, R.; Mizukami, T.; Miyata, N. Design, synthesis, enzyme-inhibitory activity, and effect on human cancer cells of a novel series of jumonji domain-containing protein 2 histone demethylase inhibitors J. Med. Chem. 2010, 53, 5629-5638
70. Suzuki, T.; Khan, M. N.; Sawada, H.; Imai, E.; Itoh, Y.; Yamatsuta, K.; Tokuda, N.; Takeuchi, J.; Seko, T.; Nakagawa, H.; Miyata, N. Design, synthesis, and biological activity of a novel series of human sirtuin-2-selective inhibitors J. Med. Chem. 2012, 55, 5760-5773
71. Paterni, I.; Bertini, S.; Granchi, C.; Tuccinardi, T.; Macchia, M.; Martinelli, A.; Caligiuri, I.; Toffoli, G.; Rizzolio, F.; Carlson, K. E.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A.; Minutolo, F. Highly selective salicylketoxime-based estrogen receptor β agonists display antiproliferative activities in a glioma model J. Med. Chem. 2015, 58, 1184-1194 10.1021/jm501829f
72. Fang, Z.; Song, Y.; Zhan, P.; Zhang, Q.; Liu, X. Conformational restriction: an effective tactic in follow-on-based drug discovery Future Med. Chem. 2014, 6, 885-901
73. Kobayashi, T.; Suemasa, A.; Igawa, A.; Ide, S.; Fukuda, H.; Abe, H.; Arisawa, M.; Minami, M.; Shuto, S. Conformationally restricted GABA with bicyclo[3.1.0]hexane backbone as the first highly selective BGT-1 inhibitor ACS Med. Chem. Lett. 2014, 5, 889-893
74. Hay, D. A.; Fedorov, O.; Martin, S.; Singleton, D. C.; Tallant, C.; Wells, C.; Picaud, S.; Philpott, M.; Monteiro, O. P.; Rogers, C. M.; Conway, S. J.; Rooney, T. P.; Tumber, A.; Yapp, C.; Filippakopoulos, P.; Bunnage, M. E.; Müller, S.; Knapp, S.; Schofield, C. J.; Brennan, P. E. Discovery and optimization of small-molecule ligands for the CBP/p300 bromodomains J. Am. Chem, Soc. 2014, 136, 9308-9319
75. Saupe, S. M.; Steinmetzer, T. A new strategy for the development of highly potent and selective plasmin inhibitors J. Med. Chem. 2012, 55, 1171-1180
76. Bastida, A.; Hidalgo, A.; Chiara, J. L.; Torrado, M.; Corzana, F.; Pérez-Cañadillas, J. M.; Groves, P.; Garcia-Junceda, E.; Gonzalez, C.; Jimenez-Barbero, J.; Asensio, J. L. Exploring the use of conformationally locked aminoglycosides as a new strategy to overcome bacterial resistance J. Am. Chem. Soc. 2006, 128, 100-116
77. Kim, J.; Kim, H.; Park, S. B. Privileged structures: efficient chemical "navigators" toward unexplored biologically relevant chemical spaces J. Am. Chem. Soc. 2014, 136, 14629-14638
78. Olsen, C. A.; Ghadiri, M. R. Discovery of potent and selective histone deacetylase inhibitors via focused combinatorial libraries of cyclic alpha3beta-tetrapeptides J. Med. Chem. 2009, 52, 7836-7846
79. Baud, M. G.; Leiser, T.; Haus, P.; Samlal, S.; Wong, A. C.; Wood, R. J.; Petrucci, V.; Gunaratnam, M.; Hughes, S. M.; Buluwela, L.; Turlais, F.; Neidle, S.; Meyer-Almes, F. J.; White, A. J.; Fuchter, M. J. Defining the mechanism of action and enzymatic selectivity of psammaplin A against its epigenetic targets J. Med. Chem. 2012, 55, 1731-1750
80. Holub, J. M.; Kirshenbaum, K. Tricks with clicks: modification of peptidomimetic oligomers via copper-catalyzed azide-alkyne [3 + 2] cycloaddition Chem. Soc. Rev. 2010, 39, 1325-1337
81. Bose, P.; Dai, Y.; Grant, S. Histone deacetylase inhibitor (HDACI) mechanisms of action: emerging insights Pharmacol. Ther. 2014, 143, 323-336
82. Suzuki, T.; Ota, Y.; Ri, M.; Bando, M.; Gotoh, A.; Itoh, Y.; Tsumoto, H.; Tatum, P. R.; Mizukami, T.; Nakagawa, H.; Iida, S.; Ueda, R.; Shirahige, K.; Miyata, N. Rapid discovery of highly potent and selective inhibitors of histone deacetylase 8 using click chemistry to generate candidate libraries J. Med. Chem. 2012, 55, 9562-9575
83. Suzuki, T.; Kasuya, Y.; Itoh, Y.; Ota, Y.; Zhan, P.; Asamitsu, K.; Nakagawa, H.; Okamoto, T.; Miyata, N. Identification of highly selective and potent histone deacetylase 3 inhibitors using click chemistry-based combinatorial fragment assembly PLoS One 2013, 8, e68669
84. Tatum, P. R.; Sawada, H.; Ota, Y.; Itoh, Y.; Zhan, P.; Ieda, N.; Nakagawa, H.; Miyata, N.; Suzuki, T. Identification of novel SIRT2-selective inhibitors using a click chemistry approach Bioorg. Med. Chem. Lett. 2014, 24, 1871-1874
85. Gehringer, M.; Forster, M.; Laufer, S. A. Solution-phase parallel synthesis of Ruxolitinib-derived janus kinase inhibitors via copper catalyzed azide-alkyne cycloaddition ACS Comb. Sci. 2015, 17, 5-10
86. Chen, Y.; Shoichet, B. K. Molecular docking and ligand specificity in fragment-based inhibitor discovery Nature Chem. Biol. 2009, 5, 358-364
87. Wagner, F. F.; Zhang, Y. L.; Fass, D. M.; Joseph, N.; Gale, J. P.; Weïwer, M.; McCarren, P.; Fisher, S. L.; Kaya, T.; Zhao, W. N.; Reis, S. A.; Hennig, K. M.; Thomas, M.; Lemercier, B. C.; Lewis, M. C.; Guan, J. S.; Moyer, M. P.; Scolnick, E.; Haggarty, S. J.; Tsai, L. H.; Holson, E. B. Kinetically selective inhibitors of histone deacetylase 2 (HDAC2) as cognition enhancers Chem. Sci. 2015, 6, 804-815
88. Zhou, J.; Li, M.; Chen, N.; Wang, S.; Luo, H. B.; Zhang, Y.; Wu, R. Computational design of a time-dependent histone deacetylase 2 selective Inhibitor ACS Chem. Biol. 2015, 10, 687-692 10.1021/cb500767c
89. Jöst, C.; Nitsche, C.; Scholz, T.; Roux, L.; Klein, C. D. Promiscuity and selectivity in covalent enzyme inhibition: a systematic study of electrophilic fragments J. Med. Chem. 2014, 57, 7590-7599
90. Arrowsmith, C. H.; Bountra, C.; Fish, P. V.; Lee, K.; Schapira, M. Epigenetic protein families: a new frontier for drug discovery Nature Rev. Drug Discovery 2012, 11, 384-400
91. Itoh, Y.; Suzuki, T.; Miyata, N. Small-molecular modulators of cancer-associated epigenetic mechanisms Mol. Biosyst. 2013, 9, 873-96
92. Suzuki, T.; Miyata, N. Epigenetic control using natural products and synthetic molecules Curr. Med. Chem. 2006, 13, 935-958