Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344

Journal of Immunology

Volumn 175, Issue 8, 2005, Pages 5370-5378

  Brodmerkel, Carrie M ^a   Huber, Reid ^a   Covington, Maryanne ^a   Diamond, Sharon ^a   Hall, Leslie ^a   Collins, Robert ^a   Leffet, Lynn ^a   Gallagher, Karen ^a   Feldman, Patricia ^a   Collier, Paul ^a   Stow, Mark ^a   Gu, Xiaomei ^a   Baribaud, Frederic ^a   Shin, Niu ^a   Thomas, Beth ^a   Burn, Tim ^a   Hollis, Greg ^a   Yeleswaram, Swamy ^a   Solomon, Kim ^a   Friedman, Steve ^a   Wang, Anlai ^a   Xue, Chu Biao ^a   Newton, Robert C ^a   Scherle, Peggy ^a   Vaddi, Kris ^a   more..

^a Experimental Station   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMOKINE RECEPTOR ANTAGONIST; CHEMOKINE RECEPTOR CCR2; G PROTEIN COUPLED RECEPTOR; INCB 3344; LIGAND; MACROPHAGE INFLAMMATORY PROTEIN 1BETA; MITOGEN ACTIVATED PROTEIN KINASE; MONOCYTE CHEMOTACTIC PROTEIN 5; PHORBOL 13 ACETATE 12 MYRISTATE; THIOGLYCOLIC ACID; UNCLASSIFIED DRUG;

ADJUVANT ARTHRITIS; ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CHEMOTAXIS; CONTROLLED STUDY; DELAYED HYPERSENSITIVITY; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG TARGETING; ENZYME PHOSPHORYLATION; FEMALE; HISTOPATHOLOGY; INFLAMMATORY DISEASE; LIGAND BINDING; MACROPHAGE; MONOCYTE; MOUSE; MULTIPLE SCLEROSIS; NONHUMAN; NUCLEOTIDE SEQUENCE; PERITONITIS; PRIORITY JOURNAL; RAT; REAL TIME POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION;

EID: 26844448558     PISSN: 00221767     EISSN: None     Source Type: Journal    
DOI: 10.4049/jimmunol.175.8.5370     Document Type: Article

References (41)

1. Kinne, R. W., R. Brauer, B. Stuhlmuller, E. Palombo-Kinne, and G. Burmester. 2000. Macrophages in rheumatoid arthritis. Arthritis Res. 2: 189-202.
2. Barrera, P., A. Blom, P. L. van Lent, L. van Bloois, J. H. Beijnen, N. van Rooiken, M. C. de Waal Malefijt, L. B. van de Putte, and W. B. van den Berg. 2000. Synovial macrophage depletion with clodronate-containing liposomes in rheumatoid arthritis. Arthritis Rheum. 43: 1951-1959.
3. Smeets, T. J. M., M. C. Kraan, M. E. van Loon, and P.-P. Tak. 2003. Tumor necrosis factor α blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue. Arthritis Rheum. 48: 2155-2162.
4. Power, C. A., and A. E. Proudfoot. 2001. The chemokine system: novel broad-spectrum therapeutic targets. Curr. Opin. Pharmacol. 1: 417-424.
5. Boring, L., J. Gosling, S. W. Chensue, S. L. Kunkel, R. V. Farese, Jr., H. E. Broxmeyer, and I. F. Charo. 1997. Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice. J. Clin. Invest. 100: 2552-2561.
6. Kurihara, T., G. Warr, J. Loy, and R. Bravo. 1997. Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor. J. Exp. Med. 186: 1757-1762.
7. Kuziel, W. A., S. J. Morgan, T. C. Dawson, S. Griffin, O. Smithies, K. Ley, and N. Maeda. 1997. Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2. Proc. Natl. Acad. Sci. USA 94: 12053-12058.
8. Lu, B., B. J. Rutledge, L. Gu, J. Fiorillo, N. W. Lukacs, S. L. Kunkel, R. North, C. Gerard, and B. J. Rollins. 1998. Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein-1-deficient mice. J. Exp. Med. 187: 601-608.
9. Fife, B. T., G. B. Huffnagle, W. A. Kuziel, and W. J. Karpus. 2000. CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J. Exp. Med. 192: 899-905.
10. Huang, D., J. Wang, O. Kivisakk, B. J. Rollins, and R. M. Ransohoff. 2001. Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis. J. Exp. Med. 193: 713-726.
11. Abbadie, C., J. A. Lindia, A. M. Cumiskey, L. B. Peterson, J. S. Mudgett, E. K. Bayne, J. A. DeMartino, D. E. MacIntyre, and M. J. Forrest. 2003. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc. Natl. Acad Sci. USA 100: 7947-7952.
12. -/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394: 894-897.
13. Gu, L., Y. Okada, S. K. Clinton, C. Gerard, G. K. Sukhova, P. Libby, and B. J. Rollins. 1998. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol. Cell 2: 275-281.
14. 2-terminal residues. J. Exp. Med. 181: 631-640.
15. Kitamoto, S., and K. Egashira. 2003. Anti-monocyte chemoattractant protein-1 gene therapy for cardiovascular diseases. Expert Rev. Cardiovasc. Ther. 1: 393-400.
16. Hasegawa, H., M. Kohno, M. Sasaki, A. Inoue, M. R. Ito, M. Terada, and K. Hieshum. 2003. Antagonist of monocyte chemoattractant protein-1 ameliorates the initiation and progression of lupus nephritis and renal vasculitis in MRL/1pr mice. Arthritis Rheum. 48: 2555-2566.
17. Gao, Z., and W. A. Metz. 2003. Unraveling the chemistry of chemokine receptor ligands. Chem. Rev. 103: 3733-3752.
18. Izikson, L., R. S. Klein, I. F. Charo, H. L. Weiner, and A. D. Luster. 2000. Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2. J. Exp. Med. 192: 1075-1080.
19. Xue, C., B. Metcalf, H. Feng, G. Cao, T. Huang, C. Zheng, D. J. Robinson, and A. Han. 3-Aminopyrrolidine derivatives as modulators of chemokine receptors. U.S. Patent Application WO2004/050024. Incyte Corporation. Filed November 2003. Published June 2004.
20. Rollins, B., A. Walz, and M. Baggiolini. 1991. Recombinant human MCP-1/JE induces chemotaxis, calcium flux and the respiratory burst in human monocytes. Blood 78: 1112-1116.
21. Gibson, U. E., C. A. Heid, and P. M. Williams. 1996. A novel method for real time quantitative RT-PCR. Genome Res. 6: 995-1001.
22. Ernst, C., Y. Zhang, P. Hancock, B. Rutledge, C. Corless, and B. Rollins. 1994. Biochemical and biologic characterization of murine monocyte chemoattractant protein-1 identification of two functional domains. J. Immunol. 152: 3541-3549.
23. Wain, J., J. Kirby, and S. Ali. 2002. Examination of mitogen-activated protein kinase and phosphoinositide 3-kinase activation by monocyte chemoattractant proteins-1, -2, -3 and -4. Clin. Exp. Immunol. 127: 436-444.
24. Ashida, N., H. Arai, M. Yamasaki, and T. Kita. 2001. Distinct signaling pathways for MCP-1 dependent integrin activation and chemotaxis. J. Biol. Chem. 276: 16555-16560.
25. Black, C. A. 1999. Delayed type hypersensitivity: current theories with an historic perspective. Dermatol. Online J. 5: 7.
26. Rottman, J. B., A. J. Slavin, R. Silva, H. Weiner, C. G. Gerard, and W. W. Hancock. 2000. Leukocyte recruitment during onset of experimental allergic encephalomyelitis is CCR1 dependent. Eur. J. Immunol. 30: 2372-2377.
27. Tran, E. H., W. A. Kuziel, and T. Owens. 2000. Induction of experimental autoimmune encephalomyelitis in C57BL/6 mice deficient in either the chemokine macrophage inflammatory protein-1α or its CCR5 receptor. Eur. J. Immunol. 30: 1410-1415.
28. Polman, C. H., C. D. Dijkstra, T. Sminia, and J.C. Koetsier. 1986. Immunohistological analysis of macrophages in the central nervous system of Lewis rats with acute experimental allergic encephalomyelitis. J. Neuroimmunol. 11: 215-222.
29. Halloran, M. M., Z. Szekanecz, N. Barquin, G. K. Haines, and A. E. Koch. 1996. Cellular adhesion molecules in rat adjuvant arthritis. Arthritis Rheum. 39: 810-819.
30. Forbes, I. T., D. G. Cooper, E. K. Dodds, D. M. B. Hickey, R. J. Ife, M. Meeson, T. Berkhout, J. Gohil, and K. Moores. 2000. CCR2B receptor antagonists: conversion of a weak HTS hit to a potent lead compound. Bioorg. Med Chem. Lett. 10: 1803-1806.
31. Mirzadegan, T., F. Diehl, B. Ebi, S. Bhakta, I. Polsky, D. McCarley, M. Mulkins, G. S. Weatherhead, J. Lapierre, J. Dankwardt, et al. 2000. Identification of the binding site for a novel class of CCR2B chemokine receptor antagonists. J. Biol. Chem. 275: 25562-25571.
32. Berkhout, T. A., F. E. Blaney, A. M. Bridges, D. G. Cooper, I. T. Forbes, A. D. Grible, P. H. E. Groot, A. Hardy, R. J. Ife, R. Kaur, et al. 2003. CCR2: characterization of the antagonist binding site from a combined receptor modeling/mutagenesis approach. J. Med. Chem. 46: 4070-4086.
33. Gong, J.-H., L. G. Ratkay, J. D. Waterfield, and I. Clark-Lewis. 1997. An Antagonist of MCP-1 inhibits arthritis in the. MRL-1pr mouse model. J. Exp. Med. 186: 131-137.
34. Youssef, S., G. Maor, G. Wildbaum, N. Grabie, A. Gour-Lavie, and N. Karin. 2000. C-C chemokine-encoding DNA vaccines enhance breakdown of tolerance to their gene products and treat ongoing adjuvant arthritis. J. Clin. Invest. 106: 361-371.
35. Youssef, S., G. Wildbaum, G. Maor, N. Lanir, A. Gour-Lavie, N. Grabie, and N. Karin. 1998. Long-lasting protective immunity to experimental autoimmune encephalomyelitis following vaccination with naked DNA encoding C-C chemokines. J. Immunol. 161: 3870-3879.
36. Ni, W., K. Egashira, S. Kitamoto, C. Kataoka, M. Koyanagi, S. Inoue, K. Imaizumi, C. Akiyama, K. Nishida, and A. Takeshita. 2001. New antimonocyte chemoattractant protein-1 gene therapy attenuates atherosclerosis in apolipoprotein E-knockout mice. Circulation 103: 2096-2101.
37. + T cells. J. Immunol. 172: 890-898.
38. Ogata, H., M. Takeya, T. Yoshimura, K. Takagi, and K. Takahashi. 1997. The role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of collagen-induced arthritis in rats. J. Pathol. 182: 106-114.
39. Kennedy, K. J., R. M. Stricter, S. L. Kunkel, N. W. Lukacs, and W. J. Karpus. 1998. Acute and relapsing experimental autoimmune encephalomyelitis are regulated by differential expression of the CC chemokines macrophage inflammatory protein-1α and monocyte chemotactic protein-1. J. Neuroimmunol. 92: 98-108.
40. Kishimoto, T. 2004. Mechanistic insights into the biology of CCR2/MCP-1 obtained through the development of anti-CCR2 therapeutic antibodies. In Chemotactic Cytokine Gordon Research Conference, September 19-24. Aussois, France.
41. Quinones, M. P., S. K. Ahuja, F. Jimenez, J. Schaefer, E. Garavito, A. Rao, G. Chenaux, R. L. Reddick, W. A. Kuziel, and S. S. Ahuja. 2004. Experimental arthritis in CC chemokine receptor 2-null mice closely mimics severe human rheumatoid arthritis. J. Clin. Invest. 113: 856-866.