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Mini-Reviews in Medicinal Chemistry

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ISSN (Online): 1875-5607

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Mini-Review Article

Approach in Improving Potency and Selectivity of Kinase Inhibitors: Allosteric Kinase Inhibitors

Author(s): Shangfei Wei, Tianming Zhao, Jie Wang and Xin Zhai*

Volume 21, Issue 8, 2021

Published on: 22 December, 2020

Page: [991 - 1003] Pages: 13

DOI: 10.2174/1389557521666201222144355

Price: $65

Abstract

Allostery is an efficient and particular regulatory mechanism to regulate protein functions. Different from conserved orthosteric sites, allosteric sites have a distinctive functional mechanism to form the complex regulatory network. In drug discovery, kinase inhibitors targeting the allosteric pockets have received extensive attention for the advantages of high selectivity and low toxicity. The approval of trametinib as the first allosteric inhibitor validated that allosteric inhibitors could be used as effective therapeutic drugs for the treatment of diseases. To date, a wide range of allosteric inhibitors have been identified. In this perspective, we outline different binding modes and potential advantages of allosteric inhibitors. In the meantime, the research processes of typical and novel allosteric inhibitors are described briefly in terms of structure-activity relationships, ligand-protein interactions, and in vitro and in vivo activity. Additionally, challenges, as well as opportunities, are also presented.

Keywords: Allosteric inhibitors, potency, selectivity, structure-activity relationships, optimization, binding mode.

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[1]
Changeux, J.P. The concept of allosteric modulation: An overview. Drug Discov. Today. Technol., 2013, 10(2), e223-e228.
[http://dx.doi.org/10.1016/j.ddtec.2012.07.007] [PMID: 24050272]
[2]
Peracchi, A.; Mozzarelli, A. Exploring and exploiting allostery: Models, evolution, and drug targeting. Biochim. Biophys. Acta, 2011, 1814(8), 922-933.
[http://dx.doi.org/10.1016/j.bbapap.2010.10.008] [PMID: 21035570]
[3]
Gunasekaran, K.; Ma, B.; Nussinov, R. Is allostery an intrinsic property of all dynamic proteins? Proteins, 2004, 57(3), 433-443.
[http://dx.doi.org/10.1002/prot.20232] [PMID: 15382234]
[4]
Lu, S.; Li, S.; Zhang, J. Harnessing allostery: A novel approach to drug discovery. Med. Res. Rev., 2014, 34(6), 1242-1285.
[http://dx.doi.org/10.1002/med.21317] [PMID: 24827416]
[5]
Nussinov, R.; Tsai, C.J. Allostery in disease and in drug discovery. Cell, 2013, 153(2), 293-305.
[http://dx.doi.org/10.1016/j.cell.2013.03.034] [PMID: 23582321]
[6]
Cohen, P. Protein kinases––the major drug targets of the twenty-first century? Nat. Rev. Drug Discov., 2002, 1(4), 309-315.
[http://dx.doi.org/10.1038/nrd773] [PMID: 12120282]
[7]
Levitzki, A. Protein kinase inhibitors as a therapeutic modality. Acc. Chem. Res., 2003, 36(6), 462-469.
[http://dx.doi.org/10.1021/ar0201207] [PMID: 12809533]
[8]
Fang, Z.; Grütter, C.; Rauh, D. Strategies for the selective regulation of kinases with allosteric modulators: Exploiting exclusive structural features. ACS Chem. Biol., 2013, 8(1), 58-70.
[http://dx.doi.org/10.1021/cb300663j] [PMID: 23249378]
[9]
Roskoski, R., Jr Classification of small molecule protein kinase inhibitors based upon the structures of their drug-enzyme complexes. Pharmacol. Res., 2016, 103, 26-48.
[http://dx.doi.org/10.1016/j.phrs.2015.10.021] [PMID: 26529477]
[10]
Cowan-Jacob, S.W.; Jahnke, W.; Knapp, S. Novel approaches for targeting kinases: Allosteric inhibition, allosteric activation and pseudokinases. Future Med. Chem., 2014, 6(5), 541-561.
[http://dx.doi.org/10.4155/fmc.13.216] [PMID: 24649957]
[11]
Lamba, V.; Ghosh, I. New directions in targeting protein kinases: Focusing upon true allosteric and bivalent inhibitors. Curr. Pharm. Des., 2012, 18(20), 2936-2945.
[http://dx.doi.org/10.2174/138161212800672813] [PMID: 22571662]
[12]
Melancon, B.J.; Hopkins, C.R.; Wood, M.R.; Emmitte, K.A.; Niswender, C.M.; Christopoulos, A.; Conn, P.J.; Lindsley, C.W. Allosteric modulation of seven transmembrane spanning receptors: Theory, practice, and opportunities for central nervous system drug discovery. J. Med. Chem., 2012, 55(4), 1445-1464.
[http://dx.doi.org/10.1021/jm201139r] [PMID: 22148748]
[13]
De Smet, F.; Christopoulos, A.; Carmeliet, P. Allosteric targeting of receptor tyrosine kinases. Nat. Biotechnol., 2014, 32(11), 1113-1120.
[http://dx.doi.org/10.1038/nbt.3028] [PMID: 25380447]
[14]
Dang, C.V.; Reddy, E.P.; Shokat, K.M.; Soucek, L. Drugging the ‘undruggable’ cancer targets. Nat. Rev. Cancer, 2017, 17(8), 502-508.
[http://dx.doi.org/10.1038/nrc.2017.36] [PMID: 28643779]
[15]
Jia, Y.; Yun, C.H.; Park, E.; Ercan, D.; Manuia, M.; Juarez, J.; Xu, C.; Rhee, K.; Chen, T.; Zhang, H.; Palakurthi, S.; Jang, J.; Lelais, G.; DiDonato, M.; Bursulaya, B.; Michellys, P.Y.; Epple, R.; Marsilje, T.H.; McNeill, M.; Lu, W.; Harris, J.; Bender, S.; Wong, K.K.; Jänne, P.A.; Eck, M.J. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature, 2016, 534(7605), 129-132.
[http://dx.doi.org/10.1038/nature17960] [PMID: 27251290]
[16]
Getlik, M.; Simard, J.R.; Termathe, M.; Grütter, C.; Rabiller, M.; van Otterlo, W.A.; Rauh, D. Fluorophore labeled kinase detects ligands that bind within the MAPK insert of p38α kinase. PLoS One, 2012, 7(7)
[http://dx.doi.org/10.1371/journal.pone.0039713] [PMID: 22768308]
[17]
McCubrey, J.A.; Milella, M.; Tafuri, A.; Martelli, A.M.; Lunghi, P.; Bonati, A.; Cervello, M.; Lee, J.T.; Steelman, L.S. Targeting the Raf/MEK/ERK pathway with small-molecule inhibitors. Curr. Opin. Investig. Drugs, 2008, 9(6), 614-630.
[PMID: 18516761]
[18]
Wright, C.J.M.; McCormack, P.L. Trametinib: First global approval. Drugs, 2013, 73(11), 1245-1254.
[http://dx.doi.org/10.1007/s40265-013-0096-1] [PMID: 23846731]
[19]
Abe, H.; Kikuchi, S.; Hayakawa, K.; Iida, T.; Nagahashi, N.; Maeda, K.; Sakamoto, J.; Matsumoto, N.; Miura, T.; Matsumura, K.; Seki, N.; Inaba, T.; Kawasaki, H.; Yamaguchi, T.; Kakefuda, R.; Nanayama, T.; Kurachi, H.; Hori, Y.; Yoshida, T.; Kakegawa, J.; Watanabe, Y.; Gilmartin, A.G.; Richter, M.C.; Moss, K.G.; Laquerre, S.G. Discovery of a highly potent and selective MEK inhibitor: GSK1120212 (JTP-74057 DMSO Solvate). ACS Med. Chem. Lett., 2011, 2(4), 320-324.
[http://dx.doi.org/10.1021/ml200004g] [PMID: 24900312]
[20]
Yamaguchi, T.; Kakefuda, R.; Tajima, N.; Sowa, Y.; Sakai, T. Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo. Int. J. Oncol., 2011, 39(1), 23-31.
[PMID: 21523318]
[21]
Long, G.V.; Stroyakovskiy, D.; Gogas, H.; Levchenko, E.; de Braud, F.; Larkin, J.; Garbe, C.; Jouary, T.; Hauschild, A.; Grob, J.J.; Chiarion Sileni, V.; Lebbe, C.; Mandalà, M.; Millward, M.; Arance, A.; Bondarenko, I.; Haanen, J.B A G.; Hansson, J.; Utikal, J.; Ferraresi, V.; Kovalenko, N.; Mohr, P.; Probachai, V.; Schadendorf, D.; Nathan, P.; Robert, C.; Ribas, A.; DeMarini, D.J.; Irani, J.G.; Casey, M.; Ouellet, D.; Martin, A-M.; Le, N.; Patel, K.; Flaherty, K. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N. Engl. J. Med., 2014, 371(20), 1877-1888.
[http://dx.doi.org/10.1056/NEJMoa1406037] [PMID: 25265492]
[22]
Robert, C.; Karaszewska, B.; Schachter, J.; Rutkowski, P.; Mackiewicz, A.; Stroiakovski, D.; Lichinitser, M.; Dummer, R.; Grange, F.; Mortier, L.; Chiarion-Sileni, V.; Drucis, K.; Krajsova, I.; Hauschild, A.; Lorigan, P.; Wolter, P.; Long, G.V.; Flaherty, K.; Nathan, P.; Ribas, A.; Martin, A.M.; Sun, P.; Crist, W.; Legos, J.; Rubin, S.D.; Little, S.M.; Schadendorf, D. Improved overall survival in melanoma with combined dabrafenib and trametinib. N. Engl. J. Med., 2015, 372(1), 30-39.
[http://dx.doi.org/10.1056/NEJMoa1412690] [PMID: 25399551]
[23]
Garnock-Jones, K.P. Cobimetinib: First Global Approval. Drugs, 2015, 75(15), 1823-1830.
[http://dx.doi.org/10.1007/s40265-015-0477-8] [PMID: 26452567]
[24]
Rice, K.D.; Aay, N.; Anand, N.K.; Blazey, C.M.; Bowles, O.J.; Bussenius, J.; Costanzo, S.; Curtis, J.K.; Defina, S.C.; Dubenko, L.; Engst, S.; Joshi, A.A.; Kennedy, A.R.; Kim, A.I.; Koltun, E.S.; Lougheed, J.C.; Manalo, J-C.L.; Martini, J-F.; Nuss, J.M.; Peto, C.J.; Tsang, T.H.; Yu, P.; Johnston, S. Novel carboxamide-based allosteric MEK inhibitors: Discovery and optimization efforts toward XL518 (GDC-0973). ACS Med. Chem. Lett., 2012, 3(5), 416-421.
[http://dx.doi.org/10.1021/ml300049d] [PMID: 24900486]
[25]
Ohren, J.F.; Chen, H.; Pavlovsky, A.; Whitehead, C.; Zhang, E.; Kuffa, P.; Yan, C.; McConnell, P.; Spessard, C.; Banotai, C.; Mueller, W.T.; Delaney, A.; Omer, C.; Sebolt-Leopold, J.; Dudley, D.T.; Leung, I.K.; Flamme, C.; Warmus, J.; Kaufman, M.; Barrett, S.; Tecle, H.; Hasemann, C.A. Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition. Nat. Struct. Mol. Biol., 2004, 11(12), 1192-1197.
[http://dx.doi.org/10.1038/nsmb859] [PMID: 15543157]
[26]
Hoeflich, K.P.; Merchant, M.; Orr, C.; Chan, J.; Den Otter, D.; Berry, L.; Kasman, I.; Koeppen, H.; Rice, K.; Yang, N-Y.; Engst, S.; Johnston, S.; Friedman, L.S.; Belvin, M. Intermittent administration of MEK inhibitor GDC-0973 plus PI3K inhibitor GDC-0941 triggers robust apoptosis and tumor growth inhibition. Cancer Res., 2012, 72(1), 210-219.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1515] [PMID: 22084396]
[27]
Cowan-Jacob, S.W.; Guez, V.; Fendrich, G.; Griffin, J.D.; Fabbro, D.; Furet, P.; Liebetanz, J.; Mestan, J.; Manley, P.W. Imatinib (STI571) resistance in chronic myelogenous leukemia: Molecular basis of the underlying mechanisms and potential strategies for treatment. Mini Rev. Med. Chem., 2004, 4(3), 285-299.
[http://dx.doi.org/10.2174/1389557043487321] [PMID: 15032675]
[28]
Storey, S. Chronic myelogenous leukaemia market. Nat. Rev. Drug Discov., 2009, 8(6), 447.
[http://dx.doi.org/10.1038/nrd2873] [PMID: 19483705]
[29]
Adrián, F.J.; Ding, Q.; Sim, T.; Velentza, A.; Sloan, C.; Liu, Y.; Zhang, G.; Hur, W.; Ding, S.; Manley, P.; Mestan, J.; Fabbro, D.; Gray, N.S. Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat. Chem. Biol., 2006, 2(2), 95-102.
[http://dx.doi.org/10.1038/nchembio760] [PMID: 16415863]
[30]
Zhang, J.M.; Adrián, F.J.; Jahnke, W.; Cowan-Jacob, S.W. Targeting wild-type and T315I Bcr-Abl by combining allosteric with ATP-site inhibitors. Nature, 2010, 463(7280), 501.
[http://dx.doi.org/10.1038/nature08675] [PMID: 20072125]
[31]
Radi, M.; Crespan, E.; Botta, G.; Falchi, F.; Maga, G.; Manetti, F.; Corradi, V.; Mancini, M.; Santucci, M.A.; Schenone, S.; Botta, M. Discovery and SAR of 1,3,4-thiadiazole derivatives as potent Abl tyrosine kinase inhibitors and cytodifferentiating agents. Bioorg. Med. Chem. Lett., 2008, 18(3), 1207-1211.
[http://dx.doi.org/10.1016/j.bmcl.2007.11.112] [PMID: 18078752]
[32]
Radi, M.; Crespan, E.; Falchi, F.; Bernardo, V.; Zanoli, S.; Manetti, F.; Schenone, S.; Maga, G.; Botta, M. Design and synthesis of thiadiazoles and thiazoles targeting the Bcr-Abl T315I mutant: From docking false positives to ATP-noncompetitive inhibitors. ChemMedChem, 2010, 5(8), 1226-1231.
[http://dx.doi.org/10.1002/cmdc.201000066] [PMID: 20509136]
[33]
Fallacara, A.L.; Tintori, C.; Radi, M.; Schenone, S.; Botta, M. Insight into the allosteric inhibition of Abl kinase. J. Chem. Inf. Model., 2014, 54(5), 1325-1338.
[PMID: 24787133]
[34]
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.
[PMID: 30137981]
[35]
Zinda, M.J.; Johnson, M.A.; Paul, J.D.; Horn, C.; Konicek, B.W.; Lu, Z.H.; Sandusky, G.; Thomas, J.E.; Neubauer, B.L.; Lai, M.T.; Graff, J.R. AKT-1, -2, and -3 are expressed in both normal and tumor tissues of the lung, breast, prostate, and colon. Clin. Cancer Res., 2001, 7(8), 2475-2479.
[PMID: 11489829]
[36]
Wu, W.I.; Voegtli, W.C.; Sturgis, H.L.; Dizon, F.P.; Vigers, G.P.A.; Brandhuber, B.J. Crystal structure of human AKT1 with an allosteric inhibitor reveals a new mode of kinase inhibition. PLoS One, 2010, 5(9)
[http://dx.doi.org/10.1371/journal.pone.0012913] [PMID: 20886116]
[37]
Lindsley, C.W.; Zhao, Z.; Leister, W.H.; Robinson, R.G.; Barnett, S.F.; Defeo-Jones, D.; Jones, R.E.; Hartman, G.D.; Huff, J.R.; Huber, H.E.; Duggan, M.E. Allosteric Akt (PKB) inhibitors: Discovery and SAR of isozyme selective inhibitors. Bioorg. Med. Chem. Lett., 2005, 15(3), 761-764.
[http://dx.doi.org/10.1016/j.bmcl.2004.11.011] [PMID: 15664853]
[38]
Hirai, H.; Sootome, H.; Nakatsuru, Y.; Miyama, K.; Taguchi, S.; Tsujioka, K.; Ueno, Y.; Hatch, H.; Majumder, P.K.; Pan, B-S.; Kotani, H. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol. Cancer Ther., 2010, 9(7), 1956-1967.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-1012] [PMID: 20571069]
[39]
Zhao, Y.Y.; Tian, Y.; Zhang, J.; Xu, F.; Yang, Y.P.; Huang, Y.; Zhao, H.Y.; Zhang, J.W.; Xue, C.; Lam, M.H.; Yan, L.; Hu, Z.H.; Dinglin, X.X.; Zhang, L. Effects of an oral allosteric AKT inhibitor (MK-2206) on human nasopharyngeal cancer in vitro and in vivo. Drug Des. Devel. Ther., 2014, 8, 1827-1837.
[http://dx.doi.org/10.2147/DDDT.S67961] [PMID: 25336925]
[40]
Ashwell, M.A.; Lapierre, J-M.; Brassard, C.; Bresciano, K.; Bull, C.; Cornell-Kennon, S.; Eathiraj, S.; France, D.S.; Hall, T.; Hill, J.; Kelleher, E.; Khanapurkar, S.; Kizer, D.; Koerner, S.; Link, J.; Liu, Y.; Makhija, S.; Moussa, M.; Namdev, N.; Nguyen, K.; Nicewonger, R.; Palma, R.; Szwaya, J.; Tandon, M.; Uppalapati, U.; Vensel, D.; Volak, L.P.; Volckova, E.; Westlund, N.; Wu, H.; Yang, R.Y.; Chan, T.C.K. Discovery and optimization of a series of 3-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amines: Orally bioavailable, selective, and potent ATP-independent Akt inhibitors. J. Med. Chem., 2012, 55(11), 5291-5310.
[http://dx.doi.org/10.1021/jm300276x] [PMID: 22533986]
[41]
Lapierre, J-M.; Eathiraj, S.; Vensel, D.; Liu, Y.; Bull, C.O.; Cornell-Kennon, S.; Iimura, S.; Kelleher, E.W.; Kizer, D.E.; Koerner, S.; Makhija, S.; Matsuda, A.; Moussa, M.; Namdev, N.; Savage, R.E.; Szwaya, J.; Volckova, E.; Westlund, N.; Wu, H.; Schwartz, B. Discovery of 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (ARQ 092): An orally bioavailable, selective, and potent allosteric AKT inhibitor. J. Med. Chem., 2016, 59(13), 6455-6469.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00619] [PMID: 27305487]
[42]
Yu, Y.; Savage, R.E.; Eathiraj, S.; Meade, J.; Wick, M.J.; Hall, T.; Abbadessa, G.; Schwartz, B. Targeting AKT1-E17K and the PI3K/AKT pathway with an allosteric AKT inhibitor, ARQ-092. PLoS One, 2015, 10(10)e0140479
[http://dx.doi.org/10.1371/journal.pone.0140479] [PMID: 26469692]
[43]
Chong, C.R.; Jänne, P.A. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nat. Med., 2013, 19(11), 1389-1400.
[http://dx.doi.org/10.1038/nm.3388] [PMID: 24202392]
[44]
To, C.; Jang, J.; Chen, T.; Park, E.; Mushajiang, M.; De Clercq, D.J.H.; Xu, M.; Wang, S.; Cameron, M.D.; Heppner, D.E.; Shin, B.H.; Gero, T.W.; Yang, A.; Dahlberg, S.E.; Wong, K-K.; Eck, M.J.; Gray, N.S.; Jänne, P.A. Single and dual targeting of mutant EGFR with an allosteric inhibitor. Cancer Discov., 2019, 9(7), 926-943.
[http://dx.doi.org/10.1158/2159-8290.CD-18-0903] [PMID: 31092401]
[45]
De Clercq, D.J.H.; Heppner, D.E.; To, C.; Jang, J.; Park, E.; Yun, C.H.; Mushajiang, M.; Shin, B.H.; Gero, T.W.; Scott, D.A.; Jänne, P.A.; Eck, M.J.; Gray, N.S. Discovery and optimization of dibenzodiazepinones as allosteric mutant-selective EGFR inhibitors. ACS Med. Chem. Lett., 2019, 10(11), 1549-1553.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00381] [PMID: 31749909]
[46]
Bartkowska, K.; Paquin, A.; Gauthier, A.S.; Kaplan, D.R.; Miller, F.D. Trk signaling regulates neural precursor cell proliferation and differentiation during cortical development. Development, 2007, 134(24), 4369-4380.
[http://dx.doi.org/10.1242/dev.008227] [PMID: 18003743]
[47]
Vaishnavi, A.; Le, A.T.; Doebele, R.C. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov., 2015, 5(1), 25-34.
[http://dx.doi.org/10.1158/2159-8290.CD-14-0765] [PMID: 25527197]
[48]
Bagal, S.K.; Omoto, K.; Blakemore, D.C.; Bungay, P.J.; Bilsland, J.G.; Clarke, P.J.; Corbett, M.S.; Cronin, C.N.; Cui, J.J.; Dias, R.; Flanagan, N.J.; Greasley, S.E.; Grimley, R.; Johnson, E.; Fengas, D.; Kitching, L.; Kraus, M.L.; McAlpine, I.; Nagata, A.; Waldron, G.J.; Warmus, J.S. Discovery of allosteric, potent, subtype selective, and peripherally restricted TrkA kinase inhibitors. J. Med. Chem., 2019, 62(1), 247-265.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00280] [PMID: 29672039]
[49]
Laurence, A.; Pesu, M.; Silvennoinen, O.; O’Shea, J. JAK kinases in health and disease: An update. Open Rheumatol. J., 2012, 6(1), 232-244.
[http://dx.doi.org/10.2174/1874312901206010232] [PMID: 23028408]
[50]
Tokarski, J.S.; Zupa-Fernandez, A.; Tredup, J.A.; Pike, K.; Chang, C.; Xie, D.; Cheng, L.; Pedicord, D.; Muckelbauer, J.; Johnson, S.R.; Wu, S.; Edavettal, S.C.; Hong, Y.; Witmer, M.R.; Elkin, L.L.; Blat, Y.; Pitts, W.J.; Weinstein, D.S.; Burke, J.R. Tyrosine kinase 2-mediated signal transduction in T lymphocytes is blocked by pharmacological stabilization of its pseudokinase domain. J. Biol. Chem., 2015, 290(17), 11061-11074.
[http://dx.doi.org/10.1074/jbc.M114.619502] [PMID: 25762719]
[51]
Burke, J R Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain. Sci. Transl. Med, 2019, 11(502), eaaw1736.
[52]
Wrobleski, S.T.; Moslin, R.; Lin, S.; Zhang, Y.; Spergel, S.; Kempson, J.; Tokarski, J.S.; Strnad, J.; Zupa-Fernandez, A.; Cheng, L.; Shuster, D.; Gillooly, K.; Yang, X.; Heimrich, E.; McIntyre, K.W.; Chaudhry, C.; Khan, J.; Ruzanov, M.; Tredup, J.; Mulligan, D.; Xie, D.; Sun, H.; Huang, C.; D’Arienzo, C.; Aranibar, N.; Chiney, M.; Chimalakonda, A.; Pitts, W.J.; Lombardo, L.; Carter, P.H.; Burke, J.R.; Weinstein, D.S. Highly selective inhibition of tyrosine kinase 2 (TYK2) for the treatment of autoimmune diseases: Discovery of the allosteric inhibitor BMS-986165. J. Med. Chem., 2019, 62(20), 8973-8995.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00444] [PMID: 31318208]
[53]
Litchfield, D.W. Protein kinase CK2: Structure, regulation and role in cellular decisions of life and death. Biochem. J., 2003, 369(Pt 1), 1-15.
[http://dx.doi.org/10.1042/bj20021469] [PMID: 12396231]
[54]
Bestgen, B.; Krimm, I.; Kufareva, I.; Kamal, A.A.M.; Seetoh, W.G.; Abell, C.; Hartmann, R.W.; Abagyan, R.; Cochet, C.; Le Borgne, M.; Engel, M.; Lomberget, T. 2-Aminothiazole derivatives as selective allosteric modulators of the protein kinase CK2.1. Identification of an allosteric binding site. J. Med. Chem., 2019, 62(4), 1803-1816.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01766] [PMID: 30689953]
[55]
Bestgen, B.; Kufareva, I.; Seetoh, W.; Abell, C.; Hartmann, R.W.; Abagyan, R.; Le Borgne, M.; Filhol, O.; Cochet, C.; Lomberget, T.; Engel, M. 2-Aminothiazole derivatives as selective allosteric modulators of the protein kinase CK2. Part 2: Structure–based optimization and investigation of effects specific to the allosteric mode of action. J. Med. Chem., 2019, 62(4), 1817-1836.
[PMID: 30689946]
[56]
Garg, R.; Benedetti, L.G.; Abera, M.B.; Wang, H.; Abba, M.; Kazanietz, M.G. Protein kinase C and cancer: What we know and what we do not. Oncogene, 2014, 33(45), 5225-5237.
[PMID: 24336328]
[57]
Abdel-Halim, M.; Diesel, B.; Kiemer, A.K.; Abadi, A.H.; Hartmann, R.W.; Engel, M. Discovery and optimization of 1,3,5-trisubstituted pyrazolines as potent and highly selective allosteric inhibitors of protein kinase C-ζ. J. Med. Chem., 2014, 57(15), 6513-6530.
[PMID: 25058929]
[58]
Hardy, J.A.; Wells, J.A. Searching for new allosteric sites in enzymes. Curr. Opin. Struct. Biol., 2004, 14(6), 706-715.
[http://dx.doi.org/10.1016/j.sbi.2004.10.009] [PMID: 15582395]
[59]
Lu, S.; Shen, Q.; Zhang, J. Allosteric methods and their applications: Facilitating the discovery of allosteric drugs and the investigation of allosteric mechanisms. Acc. Chem. Res., 2019, 52(2), 492-500.
[http://dx.doi.org/10.1021/acs.accounts.8b00570] [PMID: 30688063]
[60]
Lu, S.; He, X.; Ni, D.; Zhang, J. Allosteric modulator discovery: From serendipity to structure-based design. J. Med. Chem., 2019, 62(14), 6405-6421.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01749] [PMID: 30817889]
[61]
Sadowsky, J.D.; Burlingame, M.A.; Wolan, D.W.; McClendon, C.L.; Jacobson, M.P.; Wells, J.A. Turning a protein kinase on or off from a single allosteric site via disulfide trapping. Proc. Natl. Acad. Sci. USA, 2011, 108(15), 6056-6061.
[http://dx.doi.org/10.1073/pnas.1102376108] [PMID: 21430264]
[62]
Smith, N.J.; Milligan, G. Allostery at G protein-coupled receptor homo- and heteromers: Uncharted pharmacological landscapes. Pharmacol. Rev., 2010, 62(4), 701-725.
[http://dx.doi.org/10.1124/pr.110.002667] [PMID: 21079041]

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