2brg › Citations

Structure-based design of novel Chk1 inhibitors: insights into hydrogen bonding and protein-ligand affinity.

Foloppe N, Fisher LM, Howes R, Kierstan P, Potter A, Robertson AG, Surgenor AE
J Med Chem 48 4332-45 (2005)
Related entries: 2br1, 2brb, 2brh, 2brm, 2brn, 2bro

Cited: 41 times
EuropePMC logo PMID: 15974586

Abstract

We report the discovery, synthesis, and crystallographic binding mode of novel furanopyrimidine and pyrrolopyrimidine inhibitors of the Chk1 kinase, an oncology target. These inhibitors are synthetically tractable and inhibit Chk1 by competing for its ATP site. A chronological account allows an objective comparison of modeled compound docking modes to the subsequently obtained crystal structures. The comparison provides insights regarding the interpretation of modeling results, in relationship to the multiple reasonable docking modes which may be obtained in a kinase-ATP site. The crystal structures were used to guide medicinal chemistry efforts. This led to a thorough characterization of a pair of ligand-protein complexes which differ by a single hydrogen bond. An analysis indicates that this hydrogen bond is expected to contribute a fraction of the 10-fold change in binding affinity, adding a valuable observation to the debate about the energetic role of hydrogen bonding in molecular recognition.

Articles - 2brg mentioned but not cited (2)

  1. Discovery of novel checkpoint kinase 1 inhibitors by virtual screening based on multiple crystal structures. Li Y, Kim DJ, Ma W, Lubet RA, Bode AM, Dong Z. J Chem Inf Model 51 2904-2914 (2011)
  2. Development and validation of an improved algorithm for overlaying flexible molecules. Taylor R, Cole JC, Cosgrove DA, Gardiner EJ, Gillet VJ, Korb O. J Comput Aided Mol Des 26 451-472 (2012)


Reviews citing this publication (6)

  1. CHARMM: the biomolecular simulation program. Brooks BR, Brooks CL, Mackerell AD, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S, Caflisch A, Caves L, Cui Q, Dinner AR, Feig M, Fischer S, Gao J, Hodoscek M, Im W, Kuczera K, Lazaridis T, Ma J, Ovchinnikov V, Paci E, Pastor RW, Post CB, Pu JZ, Schaefer M, Tidor B, Venable RM, Woodcock HL, Wu X, Yang W, York DM, Karplus M. J Comput Chem 30 1545-1614 (2009)
  2. A medicinal chemist's guide to molecular interactions. Bissantz C, Kuhn B, Stahl M. J Med Chem 53 5061-5084 (2010)
  3. Aromatic rings in chemical and biological recognition: energetics and structures. Salonen LM, Ellermann M, Diederich F. Angew Chem Int Ed Engl 50 4808-4842 (2011)
  4. Virtual screening strategies in drug discovery. McInnes C. Curr Opin Chem Biol 11 494-502 (2007)
  5. Current progress in Structure-Based Rational Drug Design marks a new mindset in drug discovery. Lounnas V, Ritschel T, Kelder J, McGuire R, Bywater RP, Foloppe N. Comput Struct Biotechnol J 5 e201302011 (2013)
  6. Novel inhibitors of checkpoint kinase 1. Arrington KL, Dudkin VY. ChemMedChem 2 1571-1585 (2007)

Articles citing this publication (33)

  1. rDock: a fast, versatile and open source program for docking ligands to proteins and nucleic acids. Ruiz-Carmona S, Alvarez-Garcia D, Foloppe N, Garmendia-Doval AB, Juhos S, Schmidtke P, Barril X, Hubbard RE, Morley SD. PLoS Comput Biol 10 e1003571 (2014)
  2. Effect of Ack1 tyrosine kinase inhibitor on ligand-independent androgen receptor activity. Mahajan K, Challa S, Coppola D, Lawrence H, Luo Y, Gevariya H, Zhu W, Chen YA, Lawrence NJ, Mahajan NP. Prostate 70 1274-1285 (2010)
  3. Substantial improvements in large-scale redocking and screening using the novel HYDE scoring function. Schneider N, Hindle S, Lange G, Klein R, Albrecht J, Briem H, Beyer K, Claußen H, Gastreich M, Lemmen C, Rarey M. J Comput Aided Mol Des 26 701-723 (2012)
  4. Protoss: a holistic approach to predict tautomers and protonation states in protein-ligand complexes. Bietz S, Urbaczek S, Schulz B, Rarey M. J Cheminform 6 12 (2014)
  5. A challenging system: free energy prediction for factor Xa. Wallnoefer HG, Liedl KR, Fox T. J Comput Chem 32 1743-1752 (2011)
  6. 4-(Aminoalkylamino)-3-benzimidazole-quinolinones as potent CHK-1 inhibitors. Ni ZJ, Barsanti P, Brammeier N, Diebes A, Poon DJ, Ng S, Pecchi S, Pfister K, Renhowe PA, Ramurthy S, Wagman AS, Bussiere DE, Le V, Zhou Y, Jansen JM, Ma S, Gesner TG. Bioorg Med Chem Lett 16 3121-3124 (2006)
  7. Design, synthesis and evaluation of molecularly targeted hypoxia-activated prodrugs. O'Connor LJ, Cazares-Körner C, Saha J, Evans CN, Stratford MR, Hammond EM, Conway SJ. Nat Protoc 11 781-794 (2016)
  8. Synthesis, structural analysis, and biological evaluation of thioxoquinazoline derivatives as phosphodiesterase 7 inhibitors. Castaño T, Wang H, Campillo NE, Ballester S, González-García C, Hernández J, Pérez C, Cuenca J, Pérez-Castillo A, Martínez A, Huertas O, Gelpí JL, Luque FJ, Ke H, Gil C. ChemMedChem 4 866-876 (2009)
  9. Hydrogen Bonding of 1,2-Azaborines in the Binding Cavity of T4 Lysozyme Mutants: Structures and Thermodynamics. Lee H, Fischer M, Shoichet BK, Liu SY. J Am Chem Soc 138 12021-12024 (2016)
  10. CH-01 is a hypoxia-activated prodrug that sensitizes cells to hypoxia/reoxygenation through inhibition of Chk1 and Aurora A. Cazares-Körner C, Pires IM, Swallow ID, Grayer SC, O'Connor LJ, Olcina MM, Christlieb M, Conway SJ, Hammond EM. ACS Chem Biol 8 1451-1459 (2013)
  11. Identification of a buried pocket for potent and selective inhibition of Chk1: prediction and verification. Foloppe N, Fisher LM, Francis G, Howes R, Kierstan P, Potter A. Bioorg Med Chem 14 1792-1804 (2006)
  12. Isoxazolo[3,4-b]quinoline-3,4(1H,9H)-diones as unique, potent and selective inhibitors for Pim-1 and Pim-2 kinases: chemistry, biological activities, and molecular modeling. Tong Y, Stewart KD, Thomas S, Przytulinska M, Johnson EF, Klinghofer V, Leverson J, McCall O, Soni NB, Luo Y, Lin NH, Sowin TJ, Giranda VL, Penning TD. Bioorg Med Chem Lett 18 5206-5208 (2008)
  13. Identification of novel, in vivo active Chk1 inhibitors utilizing structure guided drug design. Massey AJ, Stokes S, Browne H, Foloppe N, Fiumana A, Scrace S, Fallowfield M, Bedford S, Webb P, Baker L, Christie M, Drysdale MJ, Wood M. Oncotarget 6 35797-35812 (2015)
  14. Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck: development of an expedient and divergent synthetic route and preliminary SAR. DiMauro EF, Newcomb J, Nunes JJ, Bemis JE, Boucher C, Buchanan JL, Buckner WH, Cheng A, Faust T, Hsieh F, Huang X, Lee JH, Marshall TL, Martin MW, McGowan DC, Schneider S, Turci SM, White RD, Zhu X. Bioorg Med Chem Lett 17 2305-2309 (2007)
  15. Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing. Reader JC, Matthews TP, Klair S, Cheung KM, Scanlon J, Proisy N, Addison G, Ellard J, Piton N, Taylor S, Cherry M, Fisher M, Boxall K, Burns S, Walton MI, Westwood IM, Hayes A, Eve P, Valenti M, de Haven Brandon A, Box G, van Montfort RL, Williams DH, Aherne GW, Raynaud FI, Eccles SA, Garrett MD, Collins I. J Med Chem 54 8328-8342 (2011)
  16. Discovery of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of potent and selective checkpoint kinase 1 inhibitors. Tong Y, Claiborne A, Stewart KD, Park C, Kovar P, Chen Z, Credo RB, Gu WZ, Gwaltney SL, Judge RA, Zhang H, Rosenberg SH, Sham HL, Sowin TJ, Lin NH. Bioorg Med Chem 15 2759-2767 (2007)
  17. Receptor-based virtual screening of EGFR kinase inhibitors from the NCI diversity database. Choowongkomon K, Sawatdichaikul O, Songtawee N, Limtrakul J. Molecules 15 4041-4054 (2010)
  18. Identification, SAR studies, and X-ray co-crystallographic analysis of a novel furanopyrimidine aurora kinase A inhibitor. Coumar MS, Tsai MT, Chu CY, Uang BJ, Lin WH, Chang CY, Chang TY, Leou JS, Teng CH, Wu JS, Fang MY, Chen CH, Hsu JT, Wu SY, Chao YS, Hsieh HP. ChemMedChem 5 255-267 (2010)
  19. Context-dependent cell cycle checkpoint abrogation by a novel kinase inhibitor. Massey AJ, Borgognoni J, Bentley C, Foloppe N, Fiumana A, Walmsley L. PLoS One 5 e13123 (2010)
  20. Synthesis and biological evaluation of 4'-(6,7-disubstituted-2,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-biphenyl-4-ol as potent Chk1 inhibitors. Tao ZF, Li G, Tong Y, Chen Z, Merta P, Kovar P, Zhang H, Rosenberg SH, Sham HL, Sowin TJ, Lin NH. Bioorg Med Chem Lett 17 4308-4315 (2007)
  21. Pharmacophore modeling and virtual screening studies of checkpoint kinase 1 inhibitors. Chen JJ, Liu TL, Yang LJ, Li LL, Wei YQ, Yang SY. Chem Pharm Bull (Tokyo) 57 704-709 (2009)
  22. Exploring the strength of a hydrogen bond as a function of steric environment using 1,2-azaborine ligands and engineered T4 lysozyme receptors. Liu Y, Liu SY. Org Biomol Chem 17 7002-7006 (2019)
  23. Combining docking-based comparative intermolecular contacts analysis and k-nearest neighbor correlation for the discovery of new check point kinase 1 inhibitors. Jaradat NJ, Khanfar MA, Khanfar MA, Habash M, Taha MO. J Comput Aided Mol Des 29 561-581 (2015)
  24. Identification of a Water-Coordinating HER2 Inhibitor by Virtual Screening Using Similarity-Based Scoring. Guo J, Collins S, Miller WT, Rizzo RC. Biochemistry 57 4934-4951 (2018)
  25. Selected arylsulphonyl pyrazole derivatives as potential Chk1 kinase ligands-computational investigations. Czaja K, Kujawski J, Kamel K, Bernard MK. J Mol Model 26 144 (2020)
  26. Discovery of 4'-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-benzonitriles and 4'-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-pyridine-2'-carbonitriles as potent checkpoint kinase 1 (Chk1) inhibitors. Tao ZF, Li G, Tong Y, Stewart KD, Chen Z, Bui MH, Merta P, Park C, Kovar P, Zhang H, Sham HL, Rosenberg SH, Sowin TJ, Lin NH. Bioorg Med Chem Lett 17 5944-5951 (2007)
  27. Investigational Hypoxia-Activated Prodrugs: Making Sense of Future Development. Su MX, Zhang LL, Huang ZJ, Shi JJ, Lu JJ. Curr Drug Targets 20 668-678 (2019)
  28. Docking-based 3D-QSAR study of pyridyl aminothiazole derivatives as checkpoint kinase 1 inhibitors. Balupuri A, Balasubramanian PK, Gadhe CG, Cho SJ. SAR QSAR Environ Res 25 651-671 (2014)
  29. Solid-phase synthesis of tetrasubstituted pyrrolo[2,3-d]pyrimidines. Lee JH, Lim HS. Org Biomol Chem 10 4229-4235 (2012)
  30. Synthesis, checkpoint kinase 1 inhibitory properties and in vitro antiproliferative activities of new pyrrolocarbazoles. Conchon E, Anizon F, Aboab B, Golsteyn RM, Léonce S, Pfeiffer B, Prudhomme M. Bioorg Med Chem 16 4419-4430 (2008)
  31. Synthesis and preliminary structure-activity relationship study of 2-aryl-2H-pyrazolo[4,3-c]quinolin-3-ones as potential checkpoint kinase 1 (Chk1) inhibitors. Malvacio I, Cuzzolin A, Sturlese M, Vera DMA, Moyano EL, Moro S. J Enzyme Inhib Med Chem 33 171-183 (2017)
  32. Efficient one-pot synthesis of novel and diverse furo[2,3-d] pyrimidinediones and thioxofuro[2,3-d] pyrimidineones by the rhodium (II) pivalate-catalyzed reactions of cyclic diazo compounds. Somai Magar KB, Lee YR, Kim SH. Mol Divers 17 679-691 (2013)
  33. Energy windows for computed compound conformers: covering artefacts or truly large reorganization energies? Foloppe N, Chen IJ. Future Med Chem 11 97-118 (2019)


Quick links