First Pharmacophore Model of CCR3 Receptor Antagonists and its Homology Model-Assisted, Stepwise Virtual Screening

Chemical Biology and Drug Design

Volumn 77, Issue 5, 2011, Pages 373-387

  Jain, Vaibhav ^a   Saravanan, Parameswaran ^a   Arvind, Akanksha ^a   Mohan, Chethampadi Gopi ^a  

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

Author keywords

CCR3 antagonists; Homology modeling; Molecular docking; Pharmacophore model; Virtual screening

Indexed keywords

CHEMOKINE RECEPTOR ANTAGONIST; CHEMOKINE RECEPTOR CCR3;

ARTICLE; BINDING SITE; COMPUTER PROGRAM; DATA BASE; HYDROGEN BOND; MATHEMATICAL MODEL; MOLECULAR DOCKING; NUCLEOTIDE SEQUENCE; PHARMACOPHORE; PRIORITY JOURNAL; SCREENING; STRUCTURAL HOMOLOGY; STRUCTURE ACTIVITY RELATION; VIRTUAL SCREENING;

AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; CATTLE; CHEMOKINE CCL11; CHO CELLS; CRICETINAE; CRICETULUS; DATABASES, FACTUAL; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; HYDROGEN BONDING; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; HYPERSENSITIVITY; INFLAMMATION; MODELS, MOLECULAR; MOLECULAR DYNAMICS SIMULATION; MOLECULAR SEQUENCE DATA; PROTEIN BINDING; RECEPTORS, CCR3; RHODOPSIN; SEQUENCE ALIGNMENT; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79954613045     PISSN: 17470277     EISSN: 17470285     Source Type: Journal    
DOI: 10.1111/j.1747-0285.2011.01088.x     Document Type: Article

References (57)

1. Scotton C.J., Wilson J.L., Milliken D., Stamp G., Balkwill F.R. (2001) Epithelial cancer cell migration a role for chemokine receptors? Cancer Res;61:4961-4965.
2. Berger E.A., Murphy P.M., Farber J.M. (1999) Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol;17:657-700.
3. Murdoch C., Finn A. (2000) Chemokine receptors and their role in inflammation and infectious diseases. Blood;95:3032-3043.
4. Griffiths-Johnson D.A., Collins P.D., Rossi A.G., Jose P.J., Williams T.J. (1993) The chemokine, eotaxin, activates guinea-pig eosinophils in vitro and causes their accumulation into the lung in vivo. Biochem Biophys Res Commun;197:1167-1172.
5. Haines H.L., Burdick G.K., Pope M.D., Strieter R.M. (1992) Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis. J Clin Invest;90:772-779.
6. Gerszten R.E., Mach F., Sauty A., Rosenzweig A., Luster A.D. (2000) Chemokines, leukocytes, and artherosclerosis. J Lab Clin Med;136:87-92.
7. Teran L.M. (2000) CCL chemokines and asthma. Immunol Today;21:235-242.
8. Murphy P.M., Baggiolini M., Charo I.F., Hebert C.A., Horuk R., Matsushima K., Miller L.H., Oppenheim J.J., Power C.A. (2000) International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev;52:145-176.
9. Ying S., Robinson D.S., Meng Q., Rottman J., Kennedy R., Ringler D.J., Mackay C.R., Daugherty B.L., Springer M.S., Durham S.R., Williams T.J., Kay A.B. (1997) Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant colocalization of eotaxin mRNA to bronchial epithelial and endothelial cells. Eur J Immunol;27:3507-3516.
10. Gleich G.J. (1990) The eosinophil and bronchial asthma: current understanding. J Allergy Clin Immunol;85:422-436.
11. Ma W., Bryce P.J., Humbles A.A., Laouini D., Yalcindag A., Alenius H., Friend D.S., Oettgen H.C., Gerard C., Geha R.S. (2002) CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. J Clin Invest;109:621-628.
12. Boehme S.A., Sullivan S.K., Crowe P.D., Santos M., Conlon P.J., Sriramarao P., Bacon K.B. (1999) Activation of mitogen-activated protein kinase regulates eotaxin-induced eosinophil migration. J Immunol;163:1611-1618.
13. Pease J.E., Wang J., Ponath P.D., Murphy P.M. (1998) The N-terminal extracellular segments of the chemokine receptors CCR1 and CCR3 are determinants for MIP-1α and eotaxin binding, respectively, but a second domain is essential for efficient receptor activation. J Biol Chem;273:19972-19976.
14. Duchesnes C.E., Murphy P.M., Williams T.J., Pease J.E. (2006) Alanine scanning mutagenesis of the chemokine receptor CCR3 reveals distinct extracellular residues involved in recognition of the eotaxin family of chemokines. Mol Immunol;43:1221-1231.
15. Wu B., Chien E.Y.T., Mol C.D., Fenalti G., Liu W., Katritch V., Abagyan R., Brooun A., Wells P., Bi F.C., Hamel D.J., Kuhn P., Handel T.M., Cherezov V., Stevens R.C. (2010) Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science;330:1066-1071.
16. Sabroe I., Peck M.J., Keulen B.J.M., Jorritsma A., Simmons G., Clapham P.R., Williams T.J., Pease J.E. (2000) A small molecule antagonist of chemokine receptors CCR1 and CCR3. J Biol Chem;275:25985-25992.
17. Suzuki K., Morokata T., Morihira K., Sato I., Takizawa S., Kaneko M., Takahashi K., Shimizu Y. (2006) In vitro and in vivo characterization of a novel CCR3 antagonist, YM-344031. Biochem Biophys Res Commun;339:1217-1223.
18. Morokata T., Suzuki K., Masunaga Y., Taguchi K., Morihira K., Sato I., Fujii M., Takiszawa S., Torii Y., Yamamoto N., Kaneko M., Yamada T., Takahashi K., Shimizu Y. (2006) A novel, selective, and orally available antagonist for CC chemokine receptor 3. J Pharmacol Exp Ther;317:244-250.
19. Vedani A., Dobler M., Dollinger H., Hasselbach K.M., Birke F., Lill M.A. (2005) Novel ligands for the chemokine receptor-3 (CCR3): a receptor-modeling study based on 5D-QSAR. J Med Chem;48:1515-1527.
20. Wise E.L., Duchesnes C., da Fonseca P.C.A., Allen R.A., Williams T.J., Pease J.E. (2007) Small molecule receptor agonists and antagonists of CCR3 provide insight into mechanisms of chemokine receptor activation. J Biol Chem;282:27935-27943.
21. Jain V., Pandey A., Gupta S., Mohan C.G. (2009) Ligand-based molecular design of 4-benzylpiperidinealkylureas and amides as CCR3 antagonists. J Mol Model;16:669-676.
22. Okada T., Sugihara M., Bondar A.N., Elstner M., Entel P., Buss V. (2004) The retinal conformation and its environment in rhodopsin in light of a new 2.2 Å crystal structure. J Mol Biol;342:571-583.
23. Sali A., Marti-Renom M.A., Stuart A.C., Fiser A., Sanchez R., Melo F. (2000) Comparative protein structure modeling of genes and genomes. Annu Rev Biophys Biomol Struct;29:291-325.
24. Laskowski R.A., MacArthur M.W., Moss D.S., Thornton J.M. (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr;26:283-291.
25. Chemical Computing Group Inc. Molecular Operating Environment (MOE 2004.03) (2004). 1255 University St. Suite 1600, Montreal, Quebec, Canada H3B 3X3: Chemical Computing Group, Inc.
26. Colovos C., Yeates T.O. (1993) Verification of protein structures: patterns of nonbonded atomic interactions. Protein Sci;2:1511-1519.
27. Sippl M.J. (1993) Recognition of errors in three-dimensional structures of proteins. Proteins;17:355-362.
28. Krautler V., Van Gunsteren W.F., Hunenberger P.H. (2001) A fast SHAKE algorithm to solve distance constraint equations for small molecules in molecular dynamics simulations. J Comput Chem;22:501-508.
29. Dhar T.G.M., Yang G., Davies P., Malley M.F., Gougoutas J.Z., Wu D.R., Barrish J.C., Carter P.H. (2009) Urea based CCR3 antagonists employing a tetrahydro-1, 3-oxazin-2-one spacer. Bioorg Med Chem Lett;19:96-99.
30. Santella J.B., Gardner D.S., Yao W., Shi C., Reddy P., Tebben A.J., DeLucca G.V., Wacker D.A., Watson P.S., Welch P.K. (2008) From rigid cyclic templates to conformationally stabilized acyclic scaffolds. Part I: the discovery of CCR3 antagonist development candidate BMS-639623 with picomolar inhibition potency against eosinophil chemotaxis. Bioorg Med Chem Lett;18:576-585.
31. Gardner D.S., Santella J.B., Tebben A.J., Batt D.G., Ko S.S., Traeger S.C., Welch P.K., Wadman E.A., Davies P., Carter P.H., Duncia J.V. (2008) From rigid cyclic templates to conformationally stabilized acyclic scaffolds. Part II: acyclic replacements for the (3S)-3-benzylpiperidine in a series of potent CCR3 antagonists. Bioorg Med Chem Lett;18:586-595.
32. Pruitt J.R., Batt D.G., Wacker D.A., Bostrom L.L., Booker S.K., McLaughlin E., Houghton G.C., Varnes J.G., Christ D.D., Covington M. (2007) CC chemokine receptor-3 (CCR3) antagonists: improving the selectivity of DPC168 by reducing central ring lipophilicity. Bioorg Med Chem Lett;17:2992-2997.
33. Watson P.S., Jiang B., Harrison K., Asakawa N., Welch P.K., Covington M., Stowell N.C., Wadman E.A., Davies P., Solomon K.A. (2006) 2, 4-Disubstituted piperidines as selective CC chemokine receptor 3 (CCR3) antagonists: synthesis and selectivity. Bioorg Med Chem Lett;16:5695-5699.
34. De Lucca G.V., Kim U.T., Vargo B.J., Duncia J.V., Santella J.B. III, Gardner D.S., Zheng C., Liauw A., Wang Z., Emmett G. (2005) Discovery of CC chemokine receptor-3 (CCR3) antagonists with picomolar potency. J Med Chem;48:2194-2211.
35. Batt D.G., Houghton G.C., Roderick J., Santella J.B., Wacker D.A., Welch P.K., Orlovsky Y.I., Wadman E.A., Trzaskos J.M., Davies P. (2005) N-Arylalkylpiperidine urea derivatives as CC chemokine receptor-3 (CCR3) antagonists. Bioorg Med Chem Lett;15:787-791.
36. Varnes J.G., Gardner D.S., Santella J.B., Duncia J.V., Estrella M., Watson P.S., Clark C.M., Ko S.S., Welch P., Covington M. (2004) Discovery of N-propylurea 3-benzylpiperidines as selective CC chemokine receptor-3 (CCR3) antagonists. Bioorg Med Chem Lett;14:1645-1649.
37. Wacker D.A., Santella I.J., Gardner D.S., Varnes J.G., Estrella M., DeLucca G.V., Ko S.S., Tanabe K., Watson P.S., Welch P.K. (2002) CCR3 antagonists: a potential new therapy for the treatment of asthma. Discovery and structure-activity relationships. Bioorg Med Chem Lett;12:1785-1789.
38. De Lucca G.V., Kim U.T., Johnson C., Vargo B.J., Welch P.K., Covington M., Davies P., Solomon K.A., Newton R.C., Trainor G.L. (2002) Discovery and structure-activity relationship of N-(ureidoalkyl)-benzyl-piperidines as potent small molecule CC chemokine receptor-3 (CCR3) antagonists. J Med Chem;45:3794-3804.
39. Smellie A., Teig S.L., Towbin P. (1995) Poling: promoting conformational variation. J Comput Chem;16:171-187.
40. Naya A., Kobayashi K., Ishikawa M., Ohwaki K., Saeki T., Noguchi K., Ohtake N. (2001) Discovery of a novel CCR3 selective antagonist. Bioorg Med Chem Lett;11:1219-1223.
41. Dhanak D., Christmann L.T., Darcy M.G., Jurewicz A.J., Keenan R.M., Lee J., Sarau H.M., Widdowson K.L., White J.R. (2001) Discovery of potent and selective phenylalanine derived CCR3 receptor antagonists. Part 1. Bioorg Med Chem Lett;11:1445-1450.
42. Dhanak D., Christmann L.T., Darcy M.G., Keenan R.M., Knight S.D., Lee J., Ridgers L.H., Sarau H.M., Shah D.H., White J.R., Zhang L. (2001) Discovery of potent and selective phenylalanine derived CCR3 receptor antagonists. Part 2. Bioorg Med Chem Lett;11:1445-1450.
43. Naya A., Kobayashi K., Ishikawa M., Ohwaki K., Saeki T., Noguchi K., Ohtake N. (2003) Structure-activity relationships of 2-(benzothiazolylthio) acetamide class of CCR3 selective antagonist. Chem Pharm Bull (Tokyo);51:697-701.
44. Sato I., Morihira K., Inami H., Kubota H., Morokata T., Suzuki K., Hamada N., Iura Y., Nitta A., Imaoka T. (2008) Synthesis and structure-activity relationships of N-{1-[(6-fluoro-2-naphthyl) methyl] piperidin-4-yl} benzamide derivatives as novel CCR3 antagonists. Bioorg Med Chem Lett;16:144-156.
45. Guner O.F., Henry D.R. (2000) Metric for analyzing hit lists and pharmacophores. In: Guner O.F., editor. Pharmacophore Perception, Development, and Use in Drug Design. La Jolla, CA, USA: International University; p. 193-210.
46. Jones G., Willett P., Glen R.C., Leach A.R., Taylor R. (1997) Development and validation of a genetic algorithm for flexible docking. J Mol Biol;267:727-748.
47. Mendonc F.L.D., Fonseca P.C.A.D., Phillips R.M., Saldanha J.W., Williams T.H., Pease J.E. (2005) Site-directed mutagenesis of CC chemokine receptor 1 reveals the mechanism of action of UCB 35625, a small molecule chemokine receptor antagonist. J Biol Chem;280:4808-4816.
48. Mirzadegan T., Diehl F., Ebi B., Bhakta S., Polsky I., McCarley D., Mulkins M., Weatherhead G.S., Lapierre J.M., Dankwardt J. (2000) Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists binding to a common chemokine receptor motif within the helical bundle. J Biol Chem;275:25562-25571.
49. Dragic T., Trkola A., Thompson D.A.D., Cormier E.G., Kajumo F.A., Maxwell E., Lin S.W., Ying W., Smith S.O., Sakmar T.P. (2000) A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proc Natl Acad Sci USA;97:5639-5644.
50. Gerlach L.O., Skerlj R.T., Bridger G.J., Schwartz T.W. (2001) Molecular interactions of cyclam and bicyclam non-peptide antagonists with the CXCR4 chemokine receptor. J Biol Chem;276:14153-14160.
51. Onuffer J.J., Horuk R. (2002) Chemokines, chemokine receptors and small-molecule antagonists: recent developments. Trends Pharmacol Sci;23:459-467.
52. Castonguay L.A., Weng Y., Adolfsen W., Di Salvo J., Kilburn R., Caldwell C.G., Daugherty B.L., Finke P.E., Hale J.J., Lynch C.L. (2003) Binding of 2-aryl-4-(piperidin-1-yl) butanamines and 1, 3, 4-trisubstituted pyrrolidines to human CCR5: a molecular modeling-guided mutagenesis study of the binding pocket. Biochemistry;42:1544-1550.
53. Tsamis F., Gavrilov S., Kajumo F., Seibert C., Kuhmann S., Ketas T., Trkola A., Palani A., Clader J.W., Tagat J.R. (2003) Analysis of the mechanism by which the small-molecule CCR5 antagonists SCH-351125 and SCH-350581 inhibit human immunodeficiency virus type 1 entry. J Virol;77:5201-5208.
54. Blanpain C., Doranz B.J., Bondue A., Govaerts C., De Leener A., Vassart G., Doms R.W., Proudfoot A., Parmentier M. (2003) The core domain of chemokines binds CCR5 extracellular domains while their amino terminus interacts with the transmembrane helix bundle. J Biol Chem;278:5179-5187.
55. Lipinski C.A. (2000) Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods;44:235-249.
56. Brelot A., Heveker N., Montes M., Alizon M. (2000) Identification of residues of CXCR4 critical for human immunodeficiency virus coreceptor and chemokine receptor activities. J Biol Chem;275:23736-23744.
57. Tian S., Choi W.T., Liu D., Pesavento J., Wang Y., An J., Sodroski J.G., Huang Z. (2005) Distinct functional sites for human immunodeficiency virus type 1 and stromal cell-derived factor 1α on CXCR4 transmembrane helical domains. J Virol;79:12667-12673.