Rational design of CCR2 antagonists: A survey of computational studies

Expert Opinion on Drug Discovery

Volumn 5, Issue 6, 2010, Pages 543-557

  Sobhia, Masilamani Elizabeth ^a   Singh, Rajesh ^a   Kare, Pavan ^a   Chavan, Swapnil ^a  

^a NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH NIPER   (India)

Author keywords

CCR2; Docking; Homology modeling; MCP 1; Molecular dynamics; QSAR; Virtual screening

Indexed keywords

2 PYRROLIDONE DERIVATIVE; 3,5 BIS(TRIFLUOROMETHYL)BENZYL ARYLGLYCINAMIDE DERIVATIVE; 4 AMINO 2 ALKYL BUTYRAMIDE DERIVATIVE; AMIDE; BENZAMIDO BENZYL TETRAHYDROPYRAN DERIVATIVE; BETA 2 ADRENERGIC RECEPTOR; BMS 741672; CHEMOKINE RECEPTOR ANTAGONIST; CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CCR2 ANTAGONIST; CYCLOHEXANE DERIVATIVE; DIAMINE DERIVATIVE; G PROTEIN COUPLED RECEPTOR; IMIDAZOLE DERIVATIVE; IRBESARTAN; MK 0812; MLN 1202; MONOCYTE CHEMOTACTIC PROTEIN 1; N [4 [[[6,7 DIHYDRO 2 (4 METHYLPHENYL) 5H BENZOCYCLOHEPTEN 8 YL]CARBONYL]AMINO]BENZYL] N,N DIMETHYL 2H TETRAHYDROPYRAN 4 AMINIUM CHLORIDE; NSC 319990; OLMESARTAN; PF 04136309; PIPERIDINE DERIVATIVE; PYRAZOLE DERIVATIVE; PYRROLIDINE DERIVATIVE; RS 504393; SB 282241; UNCLASSIFIED DRUG;

ATHEROSCLEROSIS; CELL TRANSPORT; CLINICAL TRIAL; COMPUTER AIDED DESIGN; COMPUTER MODEL; COMPUTER PROGRAM; DIABETES MELLITUS; DISEASE ASSOCIATION; DRUG DESIGN; DRUG RESEARCH; DRUG SCREENING; DRUG STRUCTURE; DRUG TARGETING; HIGH THROUGHPUT SCREENING; HUMAN; INFLAMMATION; KNOCKOUT MOUSE; MALIGNANT NEOPLASTIC DISEASE; MATHEMATICAL COMPUTING; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MONOCYTE; MULTIPLE SCLEROSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OSTEOARTHRITIS; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN FUNCTION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REVIEW; RHEUMATOID ARTHRITIS; STRUCTURAL HOMOLOGY; VASCULAR DISEASE;

EID: 77952852059     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460441.2010.482559     Document Type: Review

References (78)

1. Carter PH. Chemokine receptor antagonism as an approach to anti-inflammatory therapy: 'just right'or plain wrong? Curr Opin Chem Biol 2002;6(4):510-525
2. Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 2006;354(6):610-621
3. Lumeng CN, DeYoung SM, Bodzin JL, Saltiel AR. Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity. Diabetes 2007;56(1):16-23
4. Tsou CL, Peters W, Si Y, et al. Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. J Clin Invest 2007;117(4):902-909
5. Gerard C, Rollins BJ. Chemokines and disease. Nat Immunol 2001;2(2):108-115
6. Luster AD. Chemokines--chemotactic cytokines that mediate inflammation. N Engl J Med 1998;338(7):436-445
7. Viola A, Luster AD. Chemokines and their receptors: drug targets in immunity and inflammation. Annu Rev Pharmacol Toxicol 2008;48:171-197
8. Rajagopalan L, Rajarathnam K. Structural basis of chemokine receptor function--a model for binding affinity and ligand selectivity. Biosci Rep 2006;26(5):325-339
9. Rot A, von Andrian UH. Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Annu Rev Immunol 2004;22:891-928
10. Gu L, Tseng SC, Rollins BJ. Monocyte chemoattractant protein-1. Chemokines 1999;72:7-29
11. Newton RC, Vaddi K. Biological responses to C-C chemokines. Methods Enzymol 1997;287:174-186
12. Biswas SK, Sodhi A. In vitro activation of murine peritoneal macrophages by monocyte chemoattractant protein-1: upregulation of CD11b, production of proinflammatory cytokines, and the signal transduction pathway. J Interferon Cytokine Res 2002;22(5):527-538
13. Bischoff SC, Krieger M, Brunner T, Dahinden CA. Monocyte chemotactic protein 1 is a potent activator of human basophils. J Exp Med 1992;175(5):1271-1275
14. Chacón MR, Fernández-Real JM, Richart C, et al. Monocyte chemoattractant protein-1 in obesity and type 2 diabetes. Insulin sensitivity study. Obesity 2007;15(3):664-672
15. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007;117(1):175-184
16. Abbadie C, Lindia JA, Cumiskey AM, et al. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Sci Signal 2003;100(13):7947-7952
17. Ogata H, Takeya M, Yoshimura T, et al. The role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of collagen-induced arthritis in rats. J Pathol 1997;182(1):106-114
18. Double-Blind, randomized, placebo-controlled trial of MLN1202 on C-reactive protein levels in patients with risk factors for cardiovascular disease. Available from: http://clinicaltrialsgov/ ct2/show/NCT00715169? term=Mln1202&rank=1. [Last accessed 11 January 2010]
19. MLN1202 in treating patients with bone metastases. Available from: http:// clinicaltrialsgov/ct2/show/NCT01015560. [Last accessed 11 January 2010]
20. Proof of confidence study of CCR2 antagonist (BMS-741672) in insulin resistance. Available from: http://clinicaltrialsgov/ct2/show/ NCT00699790?term= BMS-741672&rank=2. [Last accessed 11 January 2010]
21. Randomized, double-blind, placebo-controlled, phase 2 study in subjects with osteoarthritic pain of the knee. Available from: http://clinicaltrialsgov/ ct2/show/ NCT00689273?term= PF-04136309&rank=1. [Last accessed 11 January 2010]
22. Van Lommen G, Doyon J, Coesemans E, et al. 2-Mercaptoimidazoles, a new class of potent CCR2 antagonists. Bioorg Med Chem Lett 2005;15(3):497-500
23. Butora G, Morriello GJ, Kothandaraman S, et al. 4-Amino-2-alkyl- butyramides as small molecule CCR2 antagonists with favorable pharmacokinetic properties. Bioorg Med Chem Lett 2006;16(18):4715-4722
24. Butora G, Jiao R, Parsons WH, et al. 3-Amino-1-alkyl-cyclopentane carboxamides as small molecule antagonists of the human and murine CC chemokine receptor 2. Bioorg Med Chem Lett 2007;17(13):3636-3641
25. Pinkerton AB, Huang D, Cube RV, et al. Diaryl substituted pyrazoles as potent CCR2 receptor antagonists. Bioorg Med Chem Lett 2007;17(3):807-813
26. Yang L, Zhou C, Guo L, et al. Discovery of 3, 5-bis (trifluoromethyl) benzyl L-arylglycinamide based potent CCR2 antagonists. Bioorg Med Chem Lett 2006;16(14):3735-3739
27. Lagu B, Gerchak C, Pan M, et al. Potent and selective CC-chemokine receptor-2 (CCR2) antagonists as a potential treatment for asthma. Bioorg Med Chem Lett 2007;17(15):4382-4386
28. Pasternak A, Goble SD, Vicario PP, et al. Potent heteroarylpiperidine and carboxyphenylpiperidine 1-alkyl-cyclopentane carboxamide CCR2 antagonists. Bioorg Med Chem Lett 2008;18(3):994-998
29. Moree WJ, Kataoka K, Ramirez-Weinhouse MM, et al. Small molecule antagonists of the CCR2b receptor. Part 2: discovery process and initial structure--activity relationships of diamine derivatives. Bioorg Med Chem Lett 2004;14(21):5413-5416
30. Zou D, Zhai HX, Eckman J, et al. Novel, acidic CCR2 receptor antagonists: from hit to lead. Lett Drug Des Discov 2007;4(3):185-191 (Pubitemid 46474158)
31. Dasse OA, Evans JL, Zhai HX, et al. Novel, acidic CCR2 receptor antagonists: lead optimization. Lett Drug Des Discovery 2007;4(4):263-271
32. Carter PH, Brown GD, Friedrich SR, et al. Capped diaminopropionamide-- glycine dipeptides are inhibitors of CC chemokine receptor 2 (CCR2). Bioorg Med Chem Lett 2007;17(19):5455-5461
33. Moree WJ, Kataoka K, Ramirez-Weinhouse MM, et al. Potent antagonists of the CCR2b receptor. Part 3: SAR of the (R)-3-aminopyrrolidine series. Bioorg Med Chem Lett 2008;18(6):1869-1873
34. Cherney RJ, Mo R, Meyer DT, et al. Discovery of disubstituted cyclohexanes as a new class of CC chemokine receptor 2 antagonists. J Med Chem 2008;51(4):721-724
35. Cherney RJ, Nelson DJ, Lo YC, et al. Synthesis and evaluation of cis-3, 4-disubstituted piperidines as potent CC chemokine receptor 2 (CCR2) antagonists. Bioorg Med Chem Lett 2008;18(18):5063-5065
36. Xia M, Hou C, DeMong D, et al. Substituted dipiperidine alcohols as potent CCR2 antagonists. Bioorg Med Chem Lett 2008;18(12):3562-3564
37. Xia M, Hou C, DeMong D, et al. Synthesis and structure--activity relationship of 7-azaindole piperidine derivatives as CCR2 antagonists. Bioorg Med Chem Lett 2008;18(24):6468-6470
38. Kothandaraman S, Donnely KL, Butora G, et al. Design, synthesis, and structure--activity relationship of novel CCR2 antagonists. Bioorg Med Chem Lett 2009;19(6):1830-1834
39. Cherney RJ, Brogan JB, Mo R, et al. Discovery of trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists. Bioorg Med Chem Lett 2009;19(3):597-601
40. Cherney RJ, Mo R, Meyer DT, et al. Novel sulfone-containing di-and trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists. Bioorg Med Chem Lett 2009;19:3418-3422
41. B€ohm HJ. Current computational tools for de novo ligand design. Curr Opin Biotechnol 1996;7(4):433-436
42. Wlodawer A. Rational approach to aids drug design through structural biology. Annu Rev Med 2002;53(1):595-614
43. DesJarlais RL, Seibel GL, Kuntz ID, et al. Structure-based design of nonpeptide inhibitors specific for the human immunodeficiency virus 1 protease. PNAS 1990;87:6644-6648
44. Oloff S, Mailman RB, Tropsha A. Application of validated QSAR models of D1 dopaminergic antagonists for database mining. J Med Chem 2005;48(23):7322- 7332
45. Zhang S, Wei L, Bastow K, et al. Antitumor Agents 252. Application of validated QSAR models to database mining: discovery of novel tylophorine derivatives as potential anticancer agents. J Comput Aided Mol Des 2007;21(1):97-112
46. Nair PC, Srikanth K, Sobhia ME. QSAR studies on CCR2 antagonists with chiral sensitive hologram descriptors. Bioorg Med Chem Lett 2008;18(4):1323-1330
47. Zhou C, Guo L, Parsons WH, et al. alpha-Aminothiazole-gammaaminobutanoic amides as potent, small molecule CCR2 receptor antagonists. Bioorg Med Chem Lett 2007;17(2):309-314
48. Srikanth K, Nair PC, Sobhia ME. Probing the structural and topological requirements for CCR2 antagonism: holographic QSAR for indolopiperidine derivatives. Bioorg Med Chem Lett 2008;18:1450-1456
49. Forbes IT, Cooper DG, Dodds EK, et al. CCR2B receptor antagonists: conversion of a weak HTS hit to a potent lead compound. Bioorg Med Chem Lett 2000;10(16):1803-1806
50. Witherington J, Bordas V, Cooper DG, et al. Conformationally restricted indolopiperidine derivatives as potent CCR2B receptor antagonists. Bioorg Med Chem Lett 2001;11(16):2177-2180
51. Grigorieff N, Ceska TA, Downing KH, et al. Electron-crystallographic refinement of the structure of bacteriorhodopsin. J Mol Biol 1996;259(3):393-421
52. Pebay-Peyroula E, Rummel G, Rosenbusch JP, Landau EM. X-ray structure of bacteriorhodopsin at 2.5 angstroms from microcrystals grown in lipidic cubic phases. Science 1997;277(5332):1676-1681
53. Mirzadegan T, Diehl F, Ebi B, et al. Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists. J Biol Chem 2000;275(33):25562-25571
54. Shi XF, Liu S, Xiangyu J, et al. Structural analysis of human CCR2b and primate CCR2b by molecular modeling and molecular dynamics simulation. J Mol Model 2002;8(7):217-222
55. Marshall TG, Lee RE, Marshall FE. Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b. Theor Biol Med Model 2006;3(1):1-33
56. Unger VM, Hargrave PA, Baldwin JM, Schertler GFX. Arrangement of rhodopsin transmembrane a-helices. Nature 1997;389(6647):203-205
57. Berkhout TA, Blaney FE, Bridges AM, et al. CCR2: characterization of the antagonist binding site from a combined receptor modeling/mutagenesis approach. J Med Chem 2003;46(19):4070-4086
58. Palczewski K, Kumasaka T, Hori T, et al. Crystal structure of rhodopsin: A G protein-coupled receptor. Science 2000;289(5480):739-745
59. Jaakola VP, Griffith MT, Hanson MA, et al. The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 2008;322(5905):1211-1217
60. Warne T, Serrano-Vega MJ, Baker JG, et al. Structure of a beta1-adrenergic G-protein-coupled receptor. Nature 2008;454:486-491
61. Cherezov V, Rosenbaum DM, Hanson MA, et al. High-resolution crystal structure of an engineered human 2-adrenergic G protein coupled receptor. Science 2007;318(5854):1258-1265
62. Carter PH, Tebben AJ. The use of receptor homology modeling to facilitate the design of selective chemokine receptor antagonists. Methods Enzymol 2009;461:249-279
63. Kimura SR, Tebben AJ, Langley DR. Expanding GPCR homology model binding sites via a balloon potential: a molecular dynamics refinement approach. Proteins 2008;71(4):1919-1929
64. Costanzi S. On the applicability of GPCR homology models to computer-aided drug discovery: a comparison between in silico and crystal structures of the 2-adrenergic receptor. J Med Chem 2008;51(10):2907-2914
65. Q-SiteFinder, ligand binding site prediction. Available from: http://www.modelling.leeds.ac.uk/ qsitefinder/. [Last accessed 11 January 2010]
66. ClustalW2. Available from: http:// www.ebi.ac.uk/Tools/clustalw2/ index.html. [Last accessed 2 January 2010]
67. Kitchen DB, Decornez H, Furr JR, Bajorath J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nat Rev Drug Discovery 2004;3(11):935-949
68. Hall SE, Mao A, Nicolaidou V, et al. Elucidation of binding sites of dual antagonists in the human chemokine receptors CCR2 and CCR5. Mol Pharmacol 2009;75(6):1325-1336
69. Nair PC, Sobhia ME. Fingerprint directed scaffold hopping for identification of CCR2 antagonists. J Chem Inf Model 2008;48(9):1891-1902
70. Kramer B, Rarey M, Lengauer T. Evaluation of the FLEXX incremental construction algorithm for protein--ligand docking. Proteins 1999;37(2):228-241
71. Friesner RA, Banks JL, Murphy RB, et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 2004;47(7):1739-1749
72. Sherman W, Day T, Jacobson MP, et al. Novel procedure for modeling ligand/ receptor induced fit effects. J Med Chem 2006;49(2):534-553
73. Fleishman SJ, Harrington S, Friesner RA, et al. An automatic method for predicting transmembrane protein structures using cryo-EM and evolutionary data. Biophys J 2004;87(5):3448-3459
74. Kokubo H, Okamoto Y. Prediction of transmembrane helix configurations by replica-exchange simulations. Chem Phys Lett 2004;383(3-4):397-402
75. Shacham S, Marantz Y, Bar-Haim S, et al. PREDICT modeling and in-silico screening for G-protein coupled receptors. Proteins 2004;57(1):51-86
76. Trabanino RJ, Hall SE, Vaidehi N, et al. First principles predictions of the structure and function of G-protein-coupled receptors: validation for bovine rhodopsin. Biophys J 2004;86(4):1904-1921
77. Davies JW, Glick M, Jenkins JL. Streamlining lead discovery by aligning in silico and high-throughput screening. Curr Opin Chem Biol 2006;10(4):343-351
78. Kubinyi H. Structure-based design of enzyme inhibitors and receptor ligands. Curr Opin Drug Discov Devel 1998;1:4-15