Login Register Cart 0
Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Current Frontiers

Current Fragment-to-lead Approaches Starting from the 7-azaindole: The Pharmacological Versatility of a Privileged Molecular Fragment

Author(s): Leandro Marcos Santos* and Nelson José Freitas da Silveira

Volume 23, Issue 22, 2023

Published on: 24 July, 2023

Page: [2116 - 2130] Pages: 15

DOI: 10.2174/1568026623666230718100541

Price: $65

conference banner
Abstract

Fragment-based drug discovery is one of the most powerful paradigms in the recent context of medicinal chemistry and is being widely practiced by academic and industrial researchers. Currently, azaindoles are among the most exploited molecular fragments in pharmaceutical innovation projects inspired by fragment-to-lead strategies. The 7-azaindole is the most prominent representative within this remarkable family of pyrrolopyridine fragments, as it is present in the chemical structure of several approved antitumor drugs and also of numerous therapeutic candidates. In this paper, a brief overview on existing proofs of concept in the literature will be presented, as well as some recent works that corroborate 7-azaindole as a privileged and pharmacologically versatile molecular fragment.

« Previous Next »
Graphical Abstract

[1]
Urvashi; Senthil Kumar, J.B.; Das, P.; Tandon, V. Development of azaindole-based frameworks as potential antiviral agents and their future perspectives. J Med Chem., 2022, 65, 6454-6495.
[http://dx.doi.org/10.1021/acs.jmedchem.2c00444] [PMID: 35477274]
[2]
Mohi-ud-din, R.; Pottoo, F.H.; Mir, R.H.; Mir, P.A.; Sabreen, S.; Maqbool, M.; Shah, A.J.; Shenmar, K.; Raza, S.N. A comprehensive review on journey of pyrrole scaffold against multiple therapeutic targets. Anticancer. Agents Med. Chem., 2022, 22(19), 3291-3303.
[http://dx.doi.org/10.2174/1871520622666220613140607] [PMID: 35702764]
[3]
Manaithiya, A.; Alam, O.; Sharma, V.; Naim, M.J.; Mittal, S.; Azam, F.; Husain, A.; Sheikh, A.A.; Imran, M.; Khan, I.A. Current status of novel pyridine fused derivatives as anticancer agents: An insight into future perspectives and Structure Activity Relationship (SAR). Curr. Top. Med. Chem., 2021, 21(25), 2292-2349.
[http://dx.doi.org/10.2174/1568026621666210916171015] [PMID: 34530713]
[4]
Ling, Y.; Hao, Z.Y.; Liang, D.; Zhang, C.L.; Liu, Y.F.; Wang, Y. The expanding role of pyridine and dihydropyridine scaffolds in drug design. Drug Des. Devel. Ther., 2021, 15, 4289-4338.
[http://dx.doi.org/10.2147/DDDT.S329547] [PMID: 34675489]
[5]
Wójcicka, A.; Redzicka, A. An overview of the biological activity of pyrrolo[3,4-c]pyridine derivatives. Pharmaceuticals, 2021, 14(4), 354.
[http://dx.doi.org/10.3390/ph14040354] [PMID: 33920479]
[6]
Motati, D.R.; Amaradhi, R.; Ganesh, T. Azaindole therapeutic agents. Bioorg. Med. Chem., 2020, 28(24), 115830.
[http://dx.doi.org/10.1016/j.bmc.2020.115830] [PMID: 33161343]
[7]
Sharma, N.; Anurag 7-azaindole analogues as bioactive agents and recent results. Mini Rev. Med. Chem., 2019, 19(9), 727-736.
[http://dx.doi.org/10.2174/1389557518666180928154004] [PMID: 30264679]
[8]
PubChem. Available from:https://pubchem.ncbi.nlm.nih.gov/https://pubchem.ncbi.nlm.nih.gov/ (accessed February 9, 2023)
[9]
eMolecules. Available from:https://www.emolecules.com/https://www.emolecules.com/ (accessed February 9, 2023)
[10]
ChEMBL Database. Available from:https://www.ebi.ac.uk/chembl/https://www.ebi.ac.uk/chembl/ (accessed February 9, 2023)
[11]
Kruppa, M.; Müller, T.J.J. A survey on the synthesis of variolins, meridianins, and meriolins-naturally occurring marine (aza)indole alkaloids and their semisynthetic derivatives. Molecules, 2023, 28(3), 947.
[http://dx.doi.org/10.3390/molecules28030947] [PMID: 36770618]
[12]
Zhang, J.; Dai, J.; Lan, X.; Zhao, Y.; Yang, F.; Zhang, H.; Tang, S.; Liang, G.; Wang, X.; Tang, Q. Synthesis, bioevaluation and molecular dynamics of pyrrolo-pyridine benzamide derivatives as potential antitumor agents in vitro and in vivo. Eur. J. Med. Chem., 2022, 233, 114215.
[http://dx.doi.org/10.1016/j.ejmech.2022.114215] [PMID: 35227978]
[13]
Zhao, X.Z.; Maddali, K.; Metifiot, M.; Smith, S.J.; Vu, B.C.; Marchand, C.; Hughes, S.H.; Pommier, Y.; Burke, T.R., Jr Bicyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Chem. Biol. Drug Des., 2012, 79(2), 157-165.
[http://dx.doi.org/10.1111/j.1747-0285.2011.01270.x] [PMID: 22107736]
[14]
Chhetri, B.K.; Tedbury, P.R.; Sweeney-Jones, A.M.; Mani, L.; Soapi, K.; Manfredi, C.; Sorscher, E.; Sarafianos, S.G.; Kubanek, J. Marine natural products as leads against SARS-CoV-2 infection. J. Nat. Prod., 2022, 85(3), 657-665.
[http://dx.doi.org/10.1021/acs.jnatprod.2c00015] [PMID: 35290044]
[15]
Mérour, J.Y.; Buron, F.; Plé, K.; Bonnet, P.; Routier, S. The azaindole framework in the design of kinase inhibitors. Molecules, 2014, 19(12), 19935-19979.
[http://dx.doi.org/10.3390/molecules191219935] [PMID: 25460315]
[16]
Sharma, S.; Rao, R.; Reeve, S.M.; Phelps, G.A.; Bharatham, N.; Katagihallimath, N.; Ramachandran, V.; Raveendran, S.; Sarma, M.; Nath, A.; Thomas, T.; Manickam, D.; Nagaraj, S.; Balasubramanian, V.; Lee, R.E.; Hameed P, S.; Datta, S. Azaindole based potentiator of antibiotics against Gram-negative bacteria. ACS Infect. Dis., 2021, 7(11), 3009-3024.
[http://dx.doi.org/10.1021/acsinfecdis.1c00171] [PMID: 34699190]
[17]
Tiberi, S.; du Plessis, N.; Walzl, G.; Vjecha, M.J.; Rao, M.; Ntoumi, F.; Mfinanga, S.; Kapata, N.; Mwaba, P.; McHugh, T.D.; Ippolito, G.; Migliori, G.B.; Maeurer, M.J.; Zumla, A. Tuberculosis: Progress and advances in development of new drugs, treatment regimens, and host-directed therapies. Lancet Infect. Dis., 2018, 18(7), e183-e198.
[http://dx.doi.org/10.1016/S1473-3099(18)30110-5] [PMID: 29580819]
[18]
Giblin, G.M.P.; Billinton, A.; Briggs, M.; Brown, A.J.; Chessell, I.P.; Clayton, N.M.; Eatherton, A.J.; Goldsmith, P.; Haslam, C.; Johnson, M.R.; Mitchell, W.L.; Naylor, A.; Perboni, A.; Slingsby, B.P.; Wilson, A.W. Discovery of 1-[4-(3-Chlorophenylamino)-1-methyl-1 H -pyrrolo[3,2- c ]pyridin-7-yl]-1-morpholin-4-ylmethanone (GSK554418A), a brain penetrant 5-Azaindole CB 2 agonist for the treatment of chronic pain. J. Med. Chem., 2009, 52(19), 5785-5788.
[http://dx.doi.org/10.1021/jm9009857] [PMID: 19743867]
[19]
Meanwell, N.A.; Krystal, M.R.; Nowicka-Sans, B.; Langley, D.R.; Conlon, D.A.; Eastgate, M.D.; Grasela, D.M.; Timmins, P.; Wang, T.; Kadow, J.F. Inhibitors of HIV-1 attachment: The discovery and development of temsavir and its prodrugfostemsavir. J. Med. Chem., 2018, 61(1), 62-80.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01337] [PMID: 29271653]
[20]
Kucwaj-Brysz, K.; Baltrukevich, H.; Czarnota, K.; Handzlik, J. Chemical update on the potential for serotonin 5-HT6 and 5-HT7 receptor agents in the treatment of Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2021, 49, 128275.
[http://dx.doi.org/10.1016/j.bmcl.2021.128275] [PMID: 34311086]
[21]
Jin, T.; Zhao, L.; Wang, H.P.; Huang, M.L.; Yue, Y.; Lu, C.; Zheng, Z.B. Recent advances in the discovery and development of glyoxalase I inhibitors. Bioorg. Med. Chem., 2020, 28(4), 115243.
[http://dx.doi.org/10.1016/j.bmc.2019.115243] [PMID: 31879183]
[22]
Drießen, D.; Stuhldreier, F.; Frank, A.; Stark, H.; Wesselborg, S.; Stork, B.; Müller, T.J.J. Novel meriolin derivatives as rapid apoptosis inducers. Bioorg. Med. Chem., 2019, 27(15), 3463-3468.
[http://dx.doi.org/10.1016/j.bmc.2019.06.029] [PMID: 31248707]
[23]
Crocetti, L.; Giovannoni, M.P.; Schepetkin, I.A.; Quinn, M.T.; Khlebnikov, A.I.; Cantini, N.; Guerrini, G.; Iacovone, A.; Teodori, E.; Vergelli, C. 1H-pyrrolo[2,3-b]pyridine: A new scaffold for human neutrophil elastase (HNE) inhibitors. Bioorg. Med. Chem., 2018, 26(21), 5583-5595.
[http://dx.doi.org/10.1016/j.bmc.2018.09.034] [PMID: 30385225]
[24]
Qhobosheane, M.A.; Beteck, R.M.; Baratte, B.; Robert, T.; Ruchaud, S.; Bach, S.; Legoabe, L.J. Exploration of 7-azaindole- coumaranone hybrids and their analogues as protein kinase inhibitors. Chem. Biol. Interact., 2021, 343, 109478.
[http://dx.doi.org/10.1016/j.cbi.2021.109478] [PMID: 33905741]
[25]
Sandham, D.A.; Barker, L.; Brown, L.; Brown, Z.; Budd, D.; Charlton, S.J.; Chatterjee, D.; Cox, B.; Dubois, G.; Duggan, N.; Hall, E.; Hatto, J.; Maas, J.; Manini, J.; Profit, R.; Riddy, D.; Ritchie, C.; Sohal, B.; Shaw, D.; Stringer, R.; Sykes, D.A.; Thomas, M.; Turner, K.L.; Watson, S.J.; West, R.; Willard, E.; Williams, G.; Willis, J. Discovery of fevipiprant (NVP-QAW039), a potent and selective DP2 receptor antagonist for treatment of asthma. ACS Med. Chem. Lett., 2017, 8(5), 582-586.
[http://dx.doi.org/10.1021/acsmedchemlett.7b00157] [PMID: 28523115]
[26]
Castro, M.; Kerwin, E.; Miller, D.; Pedinoff, A.; Sher, L.; Cardenas, P.; Knorr, B.; Lawrence, D.; Ossa, D.; Wang, W.; Maspero, J.F. Efficacy and safety of fevipiprant in patients with uncontrolled asthma: Two replicate, phase 3, randomised, double-blind, placebo-controlled trials (ZEAL-1 and ZEAL-2). EClinicalMedicine, 2021, 35, 100847.
[http://dx.doi.org/10.1016/j.eclinm.2021.100847] [PMID: 33997741]
[27]
Alam, R.M.; Keating, J.J. Adding more “spice” to the pot: A review of the chemistry and pharmacology of newly emerging heterocyclic synthetic cannabinoid receptor agonists. Drug Test. Anal., 2020, 12(3), 297-315.
[http://dx.doi.org/10.1002/dta.2752] [PMID: 31854124]
[28]
Wu, L.; Zhang, C.; He, C.; Qian, D.; Lu, L.; Sun, Y.; Xu, M.; Zhuo, J.; Liu, P.C.C.; Klabe, R.; Wynn, R.; Covington, M.; Gallagher, K.; Leffet, L.; Bowman, K.; Diamond, S.; Koblish, H.; Zhang, Y.; Soloviev, M.; Hollis, G.; Burn, T.C.; Scherle, P.; Yeleswaram, S.; Huber, R.; Yao, W. Discovery of pemigatinib: A potent and selective Fibroblast Growth Factor Receptor (FGFR) inhibitor. J. Med. Chem., 2021, 64(15), 10666-10679.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00713] [PMID: 34269576]
[29]
Farmer, L.J.; Ledeboer, M.W.; Hoock, T.; Arnost, M.J.; Bethiel, R.S.; Bennani, Y.L.; Black, J.J.; Brummel, C.L.; Chakilam, A.; Dorsch, W.A.; Fan, B.; Cochran, J.E.; Halas, S.; Harrington, E.M.; Hogan, J.K.; Howe, D.; Huang, H.; Jacobs, D.H.; Laitinen, L.M.; Liao, S.; Mahajan, S.; Marone, V.; Martinez-Botella, G.; McCarthy, P.; Messersmith, D.; Namchuk, M.; Oh, L.; Penney, M.S.; Pierce, A.C.; Raybuck, S.A.; Rugg, A.; Salituro, F.G.; Saxena, K.; Shannon, D.; Shlyakter, D.; Swenson, L.; Tian, S.K.; Town, C.; Wang, J.; Wang, T.; Wannamaker, M.W.; Winquist, R.J.; Zuccola, H.J. Discovery of VX-509 (decernotinib): A potent and selective Janus kinase 3 inhibitor for the treatment of autoimmune diseases. J. Med. Chem., 2015, 58(18), 7195-7216.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00301] [PMID: 26230873]
[30]
Bollag, G.; Tsai, J.; Zhang, J.; Zhang, C.; Ibrahim, P.; Nolop, K.; Hirth, P. Vemurafenib: The first drug approved for BRAF-mutant cancer. Nat. Rev. Drug Discov., 2012, 11(11), 873-886.
[http://dx.doi.org/10.1038/nrd3847] [PMID: 23060265]
[31]
Souers, A.J.; Leverson, J.D.; Boghaert, E.R.; Ackler, S.L.; Catron, N.D.; Chen, J.; Dayton, B.D.; Ding, H.; Enschede, S.H.; Fairbrother, W.J.; Huang, D.C.S.; Hymowitz, S.G.; Jin, S.; Khaw, S.L.; Kovar, P.J.; Lam, L.T.; Lee, J.; Maecker, H.L.; Marsh, K.C.; Mason, K.D.; Mitten, M.J.; Nimmer, P.M.; Oleksijew, A.; Park, C.H.; Park, C.M.; Phillips, D.C.; Roberts, A.W.; Sampath, D.; Seymour, J.F.; Smith, M.L.; Sullivan, G.M.; Tahir, S.K.; Tse, C.; Wendt, M.D.; Xiao, Y.; Xue, J.C.; Zhang, H.; Humerickhouse, R.A.; Rosenberg, S.H.; Elmore, S.W. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat. Med., 2013, 19(2), 202-208.
[http://dx.doi.org/10.1038/nm.3048] [PMID: 23291630]
[32]
Tap, W.D.; Wainberg, Z.A.; Anthony, S.P.; Ibrahim, P.N.; Zhang, C.; Healey, J.H.; Chmielowski, B.; Staddon, A.P.; Cohn, A.L.; Shapiro, G.I.; Keedy, V.L.; Singh, A.S.; Puzanov, I.; Kwak, E.L.; Wagner, A.J.; Von Hoff, D.D.; Weiss, G.J.; Ramanathan, R.K.; Zhang, J.; Habets, G.; Zhang, Y.; Burton, E.A.; Visor, G.; Sanftner, L.; Severson, P.; Nguyen, H.; Kim, M.J.; Marimuthu, A.; Tsang, G.; Shellooe, R.; Gee, C.; West, B.L.; Hirth, P.; Nolop, K.; van de Rijn, M.; Hsu, H.H.; Peterfy, C.; Lin, P.S.; Tong-Starksen, S.; Bollag, G. Structure-guided blockade of CSF1R kinase in tenosynovial giant-cell tumor. N. Engl. J. Med., 2015, 373(5), 428-437.
[http://dx.doi.org/10.1056/NEJMoa1411366] [PMID: 26222558]
[33]
Hamaguchi, H.; Amano, Y.; Moritomo, A.; Shirakami, S.; Nakajima, Y.; Nakai, K.; Nomura, N.; Ito, M.; Higashi, Y.; Inoue, T. Discovery and structural characterization of peficitinib (ASP015K) as a novel and potent JAK inhibitor. Bioorg. Med. Chem., 2018, 26(18), 4971-4983.
[http://dx.doi.org/10.1016/j.bmc.2018.08.005] [PMID: 30145050]
[34]
Byrn, R.A.; Jones, S.M.; Bennett, H.B.; Bral, C.; Clark, M.P.; Jacobs, M.D.; Kwong, A.D.; Ledeboer, M.W.; Leeman, J.R.; McNeil, C.F.; Murcko, M.A.; Nezami, A.; Perola, E.; Rijnbrand, R.; Saxena, K.; Tsai, A.W.; Zhou, Y.; Charifson, P.S. Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit. Antimicrob. Agents Chemother., 2015, 59(3), 1569-1582.
[http://dx.doi.org/10.1128/AAC.04623-14] [PMID: 25547360]
[35]
Adhikari, A.; Mandal, D.; Rana, D.; Nath, J.; Bose, A.; Sonika; Orasugh, J.T.; De, S.; Chattopadhyay, D. COVID-19 mitigation: Nanotechnological intervention, perspective, and future scope. Materials Advances, 2023, 4(1), 52-78.
[http://dx.doi.org/10.1039/D2MA00797E]
[36]
Motati, D.R.; Amaradhi, R.; Ganesh, T. Recent developments in the synthesis of azaindoles from pyridine and pyrrole building blocks. Org. Chem. Front., 2021, 8(3), 466-513.
[http://dx.doi.org/10.1039/D0QO01079K]
[37]
Kannaboina, P.; Mondal, K.; Laha, J.K.; Das, P. Recent advances in the global ring functionalization of 7-azaindoles. Chem. Commun., 2020, 56(79), 11749-11762.
[http://dx.doi.org/10.1039/D0CC04264A] [PMID: 32935671]
[38]
Perera, T.P.S.; Jovcheva, E.; Mevellec, L.; Vialard, J.; De Lange, D.; Verhulst, T.; Paulussen, C.; Van De Ven, K.; King, P.; Freyne, E.; Rees, D.C.; Squires, M.; Saxty, G.; Page, M.; Murray, C.W.; Gilissen, R.; Ward, G.; Thompson, N.T.; Newell, D.R.; Cheng, N.; Xie, L.; Yang, J.; Platero, S.J.; Karkera, J.D.; Moy, C.; Angibaud, P.; Laquerre, S.; Lorenzi, M.V. Discovery and pharmacological characterization of JNJ-42756493 (erdafitinib), a functionally selective small-molecule FGFR family inhibitor. Mol. Cancer Ther., 2017, 16(6), 1010-1020.
[http://dx.doi.org/10.1158/1535-7163.MCT-16-0589] [PMID: 28341788]
[39]
Lanman, B.A.; Allen, J.R.; Allen, J.G.; Amegadzie, A.K.; Ashton, K.S.; Booker, S.K.; Chen, J.J.; Chen, N.; Frohn, M.J.; Goodman, G.; Kopecky, D.J.; Liu, L.; Lopez, P.; Low, J.D.; Ma, V.; Minatti, A.E.; Nguyen, T.T.; Nishimura, N.; Pickrell, A.J.; Reed, A.B.; Shin, Y.; Siegmund, A.C.; Tamayo, N.A.; Tegley, C.M.; Walton, M.C.; Wang, H.L.; Wurz, R.P.; Xue, M.; Yang, K.C.; Achanta, P.; Bartberger, M.D.; Canon, J.; Hollis, L.S.; McCarter, J.D.; Mohr, C.; Rex, K.; Saiki, A.Y.; San Miguel, T.; Volak, L.P.; Wang, K.H.; Whittington, D.A.; Zech, S.G.; Lipford, J.R.; Cee, V.J. Discovery of a covalent inhibitor of KRASG12C (AMG 510) for the treatment of solid tumors. J. Med. Chem., 2020, 63(1), 52-65.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01180] [PMID: 31820981]
[40]
Schoepfer, J.; Jahnke, W.; Berellini, G.; Buonamici, S.; Cotesta, S.; Cowan-Jacob, S.W.; Dodd, S.; Drueckes, P.; Fabbro, D.; Gabriel, T.; Groell, J.M.; Grotzfeld, R.M.; Hassan, A.Q.; Henry, C.; Iyer, V.; Jones, D.; Lombardo, F.; Loo, A.; Manley, P.W.; Pellé, X.; Rummel, G.; Salem, B.; Warmuth, M.; Wylie, A.A.; Zoller, T.; Marzinzik, A.L.; Furet, P. Discovery of asciminib (ABL001), an allosteric inhibitor of the tyrosine kinase activity of BCR-ABL1. J. Med. Chem., 2018, 61(18), 8120-8135.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01040] [PMID: 30137981]
[41]
Kirsch, P.; Hartman, A.M.; Hirsch, A.K.H.; Empting, M. Concepts and core principles of fragment-based drug design. Molecules, 2019, 24(23), 4309.
[http://dx.doi.org/10.3390/molecules24234309] [PMID: 31779114]
[42]
Congreve, M.; Carr, R.; Murray, C.; Jhoti, H. A ‘Rule of Three’ for fragment-based lead discovery? Drug Discov. Today, 2003, 8(19), 876-877.
[http://dx.doi.org/10.1016/S1359-6446(03)02831-9] [PMID: 14554012]
[43]
Jhoti, H.; Williams, G.; Rees, D.C.; Murray, C.W. The ‘rule of three’ for fragment-based drug discovery: Where are we now? Nat. Rev. Drug Discov., 2013, 12(8), 644-645.
[http://dx.doi.org/10.1038/nrd3926-c1] [PMID: 23845999]
[44]
Walsh, L.; Erlanson, D.A.; de Esch, I.J.P.; Jahnke, W.; Woodhead, A.; Wren, E. Fragment-to-Lead medicinal chemistry publications in 2021. J. Med. Chem., 2023, 66(2), 1137-1156.
[http://dx.doi.org/10.1021/acs.jmedchem.2c01827] [PMID: 36622056]
[45]
Brown, N.R.; Noble, M.E.M.; Lawrie, A.M.; Morris, M.C.; Tunnah, P.; Divita, G.; Johnson, L.N.; Endicott, J.A. Effects of phosphorylation of threonine 160 on cyclin-dependent kinase 2 structure and activity. J. Biol. Chem., 1999, 274(13), 8746-8756.
[http://dx.doi.org/10.1074/jbc.274.13.8746] [PMID: 10085115]
[46]
Donald, A.; McHardy, T.; Rowlands, M.G.; Hunter, L.J.K.; Davies, T.G.; Berdini, V.; Boyle, R.G.; Aherne, G.W.; Garrett, M.D.; Collins, I. Rapid evolution of 6-phenylpurine inhibitors of protein kinase B through structure-based design. J. Med. Chem., 2007, 50(10), 2289-2292.
[http://dx.doi.org/10.1021/jm0700924] [PMID: 17451235]
[47]
Irie, T.; Sawa, M. 7-azaindole: A versatile scaffold for developing kinase inhibitors. Chem. Pharm. Bull., 2018, 66(1), 29-36.
[http://dx.doi.org/10.1248/cpb.c17-00380] [PMID: 29311509]
[48]
Kwiatkowski, J.; Liu, B.; Tee, D.H.Y.; Chen, G.; Ahmad, N.H.B.; Wong, Y.X.; Poh, Z.Y.; Ang, S.H.; Tan, E.S.W.; Ong, E.H.Q.; Nurul Dinie; Poulsen, A.; Pendharkar, V.; Sangthongpitag, K.; Lee, M.A.; Sepramaniam, S.; Ho, S.Y.; Cherian, J.; Hill, J.; Keller, T.H.; Hung, A.W. Fragment-based drug discovery of potent protein kinase C iota inhibitors. J. Med. Chem., 2018, 61(10), 4386-4396.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00060] [PMID: 29688013]
[49]
Reina-Campos, M.; Diaz-Meco, M.T.; Moscat, J. The dual roles of the atypical protein kinase cs in cancer. Cancer Cell, 2019, 36(3), 218-235.
[http://dx.doi.org/10.1016/j.ccell.2019.07.010] [PMID: 31474570]
[50]
Chavez-Pineda, O.G.; Rodriguez-Moncayo, R.; Cedillo-Alcantar, D.F.; Guevara-Pantoja, P.E.; Amador-Hernandez, J.U.; Garcia- Cordero, J.L. Microfluidic  systems  for  the  analysis  of  blood- derived molecular biomarkers. Electrophoresis, 2022, 43(16-17), 1667-1700.
[http://dx.doi.org/10.1002/elps.202200067] [PMID: 35767850]
[51]
da Silveira, N.J.F.; de Azevedo, W.F.; Guedes, R.C.; Santos, L.M.; Marcelino, R.C.; da Silva Antunes, P.; Elias, T.C. Bioinformatics approach on bioisosterism softwares to be used in drug discovery and development. Curr. Bioinform., 2022, 17(1), 19-30.
[http://dx.doi.org/10.2174/1574893616666210525150747]
[52]
Takimura, T.; Kamata, K.; Fukasawa, K.; Ohsawa, H.; Komatani, H.; Yoshizumi, T.; Takahashi, I.; Kotani, H.; Iwasawa, Y. Structures of the PKC-ι kinase domain in its ATP-bound and apo forms reveal defined structures of residues 533–551 in the C-terminal tail and their roles in ATP binding. Acta Crystallogr. D Biol. Crystallogr., 2010, 66(5), 577-583.
[http://dx.doi.org/10.1107/S0907444910005639] [PMID: 20445233]
[53]
van der Lubbe, S.C.C.; Fonseca Guerra, C. The nature of hydrogen bonds: A delineation of the role of different energy components on hydrogen bond strengths and lengths. Chem. Asian J., 2019, 14(16), asia.201900717.
[http://dx.doi.org/10.1002/asia.201900717] [PMID: 31241855]
[54]
Kenny, P.W. Hydrogen-bond donors in drug design. J. Med. Chem., 2022, 65(21), 14261-14275.
[http://dx.doi.org/10.1021/acs.jmedchem.2c01147] [PMID: 36282210]
[55]
Moinul, M.; Khatun, S.; Amin, S.A.; Jha, T.; Gayen, S. Recent trends in fragment-based anticancer drug design strategies against different targets: A mini-review. Biochem. Pharmacol., 2022, 206, 115301.
[http://dx.doi.org/10.1016/j.bcp.2022.115301] [PMID: 36265594]
[56]
Collie, G.W.; Michaelides, I.N.; Embrey, K.; Stubbs, C.J.; Börjesson, U.; Dale, I.L.; Snijder, A.; Barlind, L.; Song, K.; Khurana, P.; Phillips, C.; Storer, R.I. Structural basis for targeting the folded P-loop conformation of c-MET. ACS Med. Chem. Lett., 2021, 12(1), 162-167.
[http://dx.doi.org/10.1021/acsmedchemlett.0c00392] [PMID: 33488978]
[57]
To, K.K.W.; Cho, W.C.S. Mesenchymal epithelial transition (MET): A key player in chemotherapy resistance and an emerging target for potentiating cancer immunotherapy. Curr. Cancer Drug Targets, 2022, 22(4), 269-285.
[http://dx.doi.org/10.2174/1568009622666220307105107] [PMID: 35255791]
[58]
Ribatti, D.; Tamma, R.; Annese, T. Epithelial-mesenchymal transition in cancer: A historical overview. Transl. Oncol., 2020, 13(6), 100773.
[http://dx.doi.org/10.1016/j.tranon.2020.100773] [PMID: 32334405]
[59]
Diethelm-Varela, B. Using NMR spectroscopy in the fragment-based drug discovery of small-molecule anticancer targeted therapies. ChemMedChem, 2021, 16(5), 725-742.
[http://dx.doi.org/10.1002/cmdc.202000756] [PMID: 33236493]
[60]
Navratilova, I; Hopkins, AL Fragment screening by surface plasmon resonance. ACS Med Chem Lett., 2010, 1(1), 44-8.
[http://dx.doi.org/10.1021/ml900002k] [PMID: 24900174]
[61]
Wang, W.; Marimuthu, A.; Tsai, J.; Kumar, A.; Krupka, H.I.; Zhang, C.; Powell, B.; Suzuki, Y.; Nguyen, H.; Tabrizizad, M.; Luu, C.; West, B.L. Structural characterization of autoinhibited c-Met kinase produced by coexpression in bacteria with phosphatase. Proc. Natl. Acad. Sci., 2006, 103(10), 3563-3568.
[http://dx.doi.org/10.1073/pnas.0600048103] [PMID: 16537444]
[62]
D’Angelo, N.D.; Bellon, S.F.; Booker, S.K.; Cheng, Y.; Coxon, A.; Dominguez, C.; Fellows, I.; Hoffman, D.; Hungate, R.; Kaplan-Lefko, P.; Lee, M.R.; Li, C.; Liu, L.; Rainbeau, E.; Reider, P.J.; Rex, K.; Siegmund, A.; Sun, Y.; Tasker, A.S.; Xi, N.; Xu, S.; Yang, Y.; Zhang, Y.; Burgess, T.L.; Dussault, I.; Kim, T.S. Design, synthesis, and biological evaluation of potent c-Met inhibitors. J. Med. Chem., 2008, 51(18), 5766-5779.
[http://dx.doi.org/10.1021/jm8006189] [PMID: 18763753]
[63]
Collie, G.W. Crystal structure of c-MET bound by compound 2. 2020.
[http://dx.doi.org/10.2210/pdb7b3t/pdb]
[64]
Collie, G.W. Crystal structure of c-MET bound by compound 3. 2020.
[http://dx.doi.org/10.2210/pdb7b3v/pdb]
[65]
Collie, G.W. Crystal structure of c-MET bound by compound 6. 2020.
[http://dx.doi.org/10.2210/pdb7b40/pdb]
[66]
Collie, G.W. Crystal structure of c-MET bound by compound 7. 2020.
[http://dx.doi.org/10.2210/pdb7b41/pdb]
[67]
Rahm, F.; Viklund, J.; Trésaugues, L.; Ellermann, M.; Giese, A.; Ericsson, U.; Forsblom, R.; Ginman, T.; Günther, J.; Hallberg, K.; Lindström, J.; Persson, L.B.; Silvander, C.; Talagas, A.; Díaz-Sáez, L.; Fedorov, O.; Huber, K.V.M.; Panagakou, I.; Siejka, P.; Gorjánácz, M.; Bauser, M.; Andersson, M. Creation of a novel class of potent and selective MutT homologue 1 (MTH1) inhibitors using fragment-based screening and structure-based drug design. J. Med. Chem., 2018, 61(6), 2533-2551.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01884] [PMID: 29485874]
[68]
Carreras-Puigvert, J; Zitnik, M; Jemth, A-S; Carter, M; Unterlass, J.E; Hallström, B; Loseva, O; Karem, Z; Calderón-Montaño, J.M; Lindskog, C; Edqvist, P-H; Matuszewski, DJ; Blal, HA; Berntsson, RPA; Häggblad, M; Martens, U; Studham, M; Lundgren, B; Wählby, C; Sonnhammer, ELL; Lundberg, E; Stenmark, P; Zupan, B; Helleday, T A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family. Nat Commun., 2017, 8(1), 1541.
[http://dx.doi.org/10.1038/s41467-017-01642-w] [PMID: 29142246]
[69]
Perrin, J.; Werner, T.; Kurzawa, N.; Rutkowska, A.; Childs, D.D.; Kalxdorf, M.; Poeckel, D.; Stonehouse, E.; Strohmer, K.; Heller, B.; Thomson, D.W.; Krause, J.; Becher, I.; Eberl, H.C.; Vappiani, J.; Sevin, D.C.; Rau, C.E.; Franken, H.; Huber, W.; Faelth-Savitski, M.; Savitski, M.M.; Bantscheff, M.; Bergamini, G. Identifying drug targets in tissues and whole blood with thermal-shift profiling. Nat. Biotechnol., 2020, 38(3), 303-308.
[http://dx.doi.org/10.1038/s41587-019-0388-4] [PMID: 31959954]
[70]
Viklund, J.; Talagas, A.; Tresaugues, L. Complex between MTH1 and compound 1 (a 7-azaindole-4-ester derivative). 2018.
[http://dx.doi.org/10.2210/pdb6f20/pdb]
[71]
Ellermann, M.; Eheim, A.; Rahm, F.; Viklund, J.; Guenther, J.; Andersson, M.; Ericsson, U.; Forsblom, R.; Ginman, T.; Lindström, J.; Silvander, C.; Trésaugues, L.; Giese, A.; Bunse, S.; Neuhaus, R.; Weiske, J.; Quanz, M.; Glasauer, A.; Nowak-Reppel, K.; Bader, B.; Irlbacher, H.; Meyer, H.; Queisser, N.; Bauser, M.; Haegebarth, A.; Gorjánácz, M. Novel class of potent and cellularly active inhibitors devalidates MTH1 as broad-spectrum cancer target. ACS Chem. Biol., 2017, 12(8), 1986-1992.
[http://dx.doi.org/10.1021/acschembio.7b00370] [PMID: 28679043]
[72]
Samaranayake, G.; Huynh, M.; Rai, P. MTH1 as a chemotherapeutic target: The elephant in the room. Cancers, 2017, 9(12), 47.
[http://dx.doi.org/10.3390/cancers9050047] [PMID: 28481306]
[73]
Ban, T.A. The role of serendipity in drug discovery. Dialogues Clin. Neurosci., 2006, 8(3), 335-344.
[http://dx.doi.org/10.31887/DCNS.2006.8.3/tban] [PMID: 17117615]
[74]
Bivik Eding, C.; Köhler, I.; Verma, D.; Sjögren, F.; Bamberg, C.; Karsten, S.; Pham, T.; Scobie, M.; Helleday, T.; Warpman Berglund, U.; Enerbäck, C. MTH1 inhibitors for the treatment of psoriasis. J. Invest. Dermatol., 2021, 141(8), 2037-2048.e4.
[http://dx.doi.org/10.1016/j.jid.2021.01.026] [PMID: 33676948]
[75]
Karsten, S.; Fiskesund, R.; Zhang, X.M.; Marttila, P.; Sanjiv, K.; Pham, T.; Rasti, A.; Bräutigam, L.; Almlöf, I.; Marcusson-Ståhl, M.; Sandman, C.; Platzack, B.; Harris, R.A.; Kalderén, C.; Cederbrant, K.; Helleday, T.; Warpman Berglund, U. MTH1 as a target to alleviate T cell driven diseases by selective suppression of activated T cells. Cell Death Differ., 2022, 29(1), 246-261.
[http://dx.doi.org/10.1038/s41418-021-00854-4] [PMID: 34453118]
[76]
Karsten, S. Targeting the DNA repair enzymes MTH1 and OGG1 as a novel approach to treat inflammatory diseases. Basic Clin. Pharmacol. Toxicol., 2022, 131(2), 95-103.
[http://dx.doi.org/10.1111/bcpt.13765] [PMID: 35708697]

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