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郭宗儒:从精准医学谈药物设计的微观结构 [2] Huang WS, Metcalf CA, Sundaramoorthi R, et al. Discovery [8] quelin G Charlton SJ. Long-lasting target binding and of 3-2-(imidazo[ 1, 2-b ]pyridazin-3-yl)ethynyl]-4-methyl-N-44. rebinding echanisms to prolong in vivo drug action J Br J Pharmacol. 2010. 161: 488 potent, o [9 Kruse AC, Hu X, Kobilka BK, et al. Muscarinic acetylcho- breakpoint cluster region-abelson(BCR-ABL) kinase including line receptor X-ray structures: potential implications for drug the T315I gatekeeper mutant []. J Med Chem, 2010, 53: development [] Curr Opin Pharmacol, 2014, 16: 24-30 [10 Fernades A, Scott R. Dehyd 3] Tie YPl, Boross YF, Wang L, et al. High resolution crystal signal for protein interaction []. Biophys J, 2003, 85: 1914 structures of HIV-l protease with a potent non-peptide inhibitor (UlC-94017)active against multidrug- resistant clinical strains [11 Demetri GD. Structural reengineering of imatinib to decrease - J Mol Biol,2004,38:34l-352 ardiac risk in cancer therapy []. J Clin Invest, 2007, 117 14] Leonis G Czyznikowska Z, Megariotis G Computational 3650-3653 studies of darunavir into HIV-1 protease and dMPC bilayer [12 Fernandez A, SanguinoA, Peng Z, et al. An anticancer c-Kit kinase inhibitor is reengineered to make it more active and less flaps []. J Chen Inf Model, 2012, 52: 1542-1558 cardiotoxic [ J]. J Clin Invest, 2007, 117: 4044-4054 [5] Deng H, Sun H, Fang Y. Label-free cell phenotypic assessment [13 Harris PA, King BW, Bandyopadhyay D, et al. DNA-encoded of the biased agonism and efficacy of agonists at the endogenous library screening identifies benzo[b][ 1, 4 ]oxazepin-4-ones as M3 receptors J]. J Pharmacol Toxicol Methods, highly potent and monoselective receptor interacting protein I 2013,68:323-333 kinase inhibitors ] J Med Chem, 2016, 59: 2163-2178 6] Matthews PM, Rabiner EA, Passchier J, et al. Positron [14 Berger SB, Hamis P, Nagilla R, et al. Characterization of emission tomography molecular imaging or drug development GSK963: a structurally distinct, potent and selective inhibitor of U]. Br J Clin Pharmacol, 2012, 73: 175-186 RIPI kinase [J]. Cell Death Discov, 2015, 1: 15009 [7 Schneider EV, Bottcher J, Huber R, et al. Structure-kinetic [15] Arico-Muendel CC. From haystack to needle: finding value relationship study of CDK8/CycC speci fic compounds with DNA encoded library technology at GSk []. Med Chem Proc Natl Acad Sci USA, 2013, 110: 8081-8086. Commun,2016.DO:10.1039C6MD00341A.郭宗儒: 从精准医学谈药物设计的微观结构 · 79 · [2] Huang WS, Metcalf CA, Sundaramoorthi R, et al. Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl- N-{4- [(4-methylpiperazin-1-yl)-methyl]-3-(trifluoromethyl)phenyl} benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant [J]. J Med Chem, 2010, 53: 4701−4719. [3] Tie YPI, Boross YF, Wang L, et al. High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multidrug-resistant clinical strains [J]. J Mol Biol, 2004, 338:341 −352. [4] Leonis G, Czyznikowska Z, Megariotis G. Computational studies of darunavir into HIV-1 protease and DMPC bilayer: necessary conditions for effective binding and the role of the flaps [J]. J Chen Inf Model, 2012, 52: 1542 −1558. [5] Deng H, Sun H, Fang Y. Label-free cell phenotypic assessment of the biased agonism and efficacy of agonists at the endogenous muscarinic M3 receptors [J]. J Pharmacol Toxicol Methods, 2013, 68: 323−333. [6] Matthews PM, Rabiner EA, Passchier J, et al. Positron emission tomography molecular imaging or drug development [J]. Br J Clin Pharmacol, 2012, 73: 175 −186. [7] Schneider EV, Böttcher J, Huber R, et al. Structure-kinetic relationship study of CDK8/CycC speci fic compounds [J]. Proc Natl Acad Sci USA, 2013, 110: 8081−8086. [8] Vauquelin G, Charlton SJ. Long-lasting target binding and rebinding as mechanisms to prolong in vivo drug action [J]. Br J Pharmacol, 2010, 161: 488 −508. [9] Kruse AC, Hu JX, Kobilka BK, et al. Muscarinic acetylcho￾line receptor X-ray structures: potential implications for drug development [J]. Curr Opin Pharmacol, 2014, 16: 24 −30. [10] Fernades A, Scott R. Dehydron: a structurally encoded signal for protein interaction [J]. Biophys J, 2003, 85: 1914 − 1928. [11] Demetri GD. Structural reengineering of imatinib to decrease cardiac risk in cancer therapy [J]. J Clin Invest, 2007, 117: 3650−3653. [12] Fernández A, SanguinoA, Peng Z, et al. An anticancer c-Kit kinase inhibitor is reengineered to make it more active and less cardiotoxic [J]. J Clin Invest, 2007, 117: 4044 −4054. [13] Harris PA, King BW, Bandyopadhyay D, et al. DNA-encoded library screening identifies benzo[b][1,4]oxazepin-4-ones as highly potent and monoselective receptor interacting protein 1 kinase inhibitors [J]. J Med Chem, 2016, 59: 2163 −2178. [14] Berger SB, Harris P, Nagilla R, et al. Characterization of GSK′963: a structurally distinct, potent and selective inhibitor of RIP1 kinase [J]. Cell Death Discov, 2015, 1: 15009. [15] Arico-Muendel CC. From haystack to needle: finding value with DNA encoded library technology at GSK [J]. Med Chem Commun, 2016. DOI: 10.1039/C6MD00341A
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