Studies with an orally bioavailable αV integrin antagonist in animal models of ocular vasculopathy: Retinal neovascularization in mice and retinal vascular permeability in diabetic rats

Journal of Pharmacology and Experimental Therapeutics

Volumn 324, Issue 3, 2008, Pages 894-901

  Santulli, Rosemary J ^a   Kinney, William A ^a   Ghosh, Shyamali ^a   DeCorte, Bart L ^a   Liu, Li ^a   Tuman, Robert W A ^a   Zhou, Zhao ^a   Huebert, Norman ^a   Bursell, Sven E ^e   Clermont, Alan C ^e   Grant, Maria B ^c   Shaw, Lynn C ^c   Mousa, Shaker A ^d   Galemmo Jr , Robert A ^a,b   Johnson, Dana L ^a   Maryanoff, Bruce E ^a   Damiano, Bruce P ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

^b Neuromed Pharmaceuticals   (Canada)

^c UNIVERSITY OF FLORIDA   (United States)

^d ALBANY COLLEGE OF PHARMACY AND HEALTH SCIENCES   (United States)

^e JOSLIN DIABETES CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3,4 TETRAHYDRO BETA [[1 [ OXO 3 (1,5,6,7 TETRAHYDRO 1,8 NAPHTHYRIDIN 2 YL)PROPYL] 4 PIPERIDINYL]METHYL] 3 QUINOLINE PROPANOIC ACID; ALPHA5 INTEGRIN; ALPHAVBETA5 INTEGRIN; FIBROBLAST GROWTH FACTOR; JNK 26076713; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; VASCULOTROPIN; VERY LATE ACTIVATION ANTIGEN 5; VITRONECTIN; VITRONECTIN RECEPTOR;

ANGIOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD VESSEL PERMEABILITY; CELL ADHESION; CELL MIGRATION; CONTROLLED STUDY; DIABETES MELLITUS; DISTRIBUTION VOLUME; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG INHIBITION; DRUG STRUCTURE; ENDOTHELIUM CELL; EYE DISEASE; HUMAN; HUMAN CELL; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; RETINA NEOVASCULARIZATION; VASCULAR DISEASE;

ADMINISTRATION, ORAL; ANGIOGENESIS INHIBITORS; ANIMALS; BIOLOGICAL AVAILABILITY; CAPILLARY PERMEABILITY; CELL LINE; CHICK EMBRYO; DIABETES MELLITUS, EXPERIMENTAL; DIABETIC RETINOPATHY; DISEASE MODELS, ANIMAL; FEMALE; HUMANS; INTEGRIN ALPHAV; MALE; MICE; MICE, INBRED C57BL; NAPHTHYRIDINES; PREGNANCY; QUINOLINES; RATS; RATS, LONG-EVANS; RATS, SPRAGUE-DAWLEY; RETINAL NEOVASCULARIZATION;

EID: 40849105041     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.107.131656     Document Type: Article

References (44)

1. Abiko T, Abiko A, Clermont AC, Shoelson B, Horio N, Takahashi J, Adamis AP, King GL, and Bursell SE (2003) Characterization of retinal leukostasis and hemodynamics in insulin resistance and diabetes. Diabetes 52:829-837.
2. Bates RC (2005) Colorectal cancer progression; integrin alphavbeta6 and the epithelial-mesenchymal transition (EMT). Cell Cycle 4:1350-1352.
3. Cai W and Chen X (2006) Anti-angiogenic cancer therapy based on integrin αvβ3 antagonism. Anticancer Agents Med Chem 6:407-428.
4. Chavakis E, Riecke B, Lin J, Linn T, Bretzel RG, Preissner KT, Brownlee M and Hammes HP (2002) Kinetics of integrin expression in the mouse model of proliferative retinopathy and success of secondary intervention with cyclic RGD peptides. Diabetologia 45:262-267.
5. Clemmons DR and Maile LA (2005) Interaction between insulin-like growth factor-I receptor and alphaVbeta3 integrin linked signaling pathways: cellular responses to changes in multiple signaling inputs. Mol Endocrinol 19:1-11.
6. Eliceiri BP and Cheresh DA (1998) The role of alphav integrins during angiogenesis. Mol Med 4:741-750.
7. Freund KB, Yannuzzi LA, and Sorenson JA (1993) Age-related macular degeneration and choroidal neovascularization. Am J Ophthalmol 115:786-791.
8. Friedlander M, Theesfeld CL, Sugita M, Fruttiger M, Thomas MA, Chang S, and Cheresh DA (1996) Involvement of integrins alpha v beta 3 and alpha v beta 5 in ocular neovascular diseases. Proc Natl Acad Sci U S A 93:9764-9769.
9. 3 integrin antagonists with enhanced oral bioavailability. Bioorg Med Chem Lett 14:5937-5941.
10. Grant MB, Afzal A, Spoerri P, Pan H, Shaw LC, and Mames RN (2004) The role of growth factors in the pathogenesis of diabetic retinopathy. Expert Opin Investig Drugs 13:1275-1293.
11. Häkkinen L, Koivisto L, Gardner H, Saarialho-Kere U, Carroll JM, Lakso M, Rauvala H, Laato M, Heino J, and Larjava H (2004) Increased expression of β6-integrin in skin leads to spontaneous development of chronic wounds. Am J Pathol 164:229-242.
12. Hodivala-Dilke KM, Reynolds AR, and Reynolds LE (2003) Integrins in angiogenesis: multitalented molecules in a balancing act. Cell Tissue Res 314:131-144.
13. Kamizuru HKH, Yasukawa T, Tabata Y, Honda Y, Ogura Y (2001) Monoclonal antibody-mediated drug targeting to choroidal neovascularization in the rat. Invest Ophthalmol Vis Sci 42:2664-2672.
14. 5 integrin antagonist. Enantioselective synthesis and stereochemical studies. J Org Chem, in press.
15. Klein R, Klein BE, Moss SE, and Cruickshanks KJ (1994) The Wisconsin Epidemiologic Study of diabetic retinopathy. XIV. Ten-year incidence and progression of diabetic retinopathy. Arch Ophthalmol 112:1217- 1228.
16. Lim EH, Danthi N, Bednarski M, and Li KCP (2005) A review: integrin alphavbeta3-targeted molecular imaging and therapy in angiogenesis. Nanomedicine 1:110-114.
17. Ljubimov AV, Burgeson RE, Butkowski RJ, Couchman JR, Zardi L, Ninomiya Y, Sado Y, Huang Z-S, Nesburn AB, and Kenney MC (1996) Basement membrane abnormalities in human eyes with diabetic retinopathy. J Histochem Cytochem 44:1469-1479.
18. Luci DK, Santulli RJ, Gauthier DA, Tounge BA, Ghosh S, Proost JC, Kinney WA, De Corte B, Galemmo RA Jr, Lewis JM, et al. (2004) A concise synthesis of an indenopyrrolidine-based dual alphavbeta3/alphavbeta5 integrin antagonist. Heterocycles 62:543-557.
19. Luna J, Tobe T, Mousa SA, Reilly TM, and Campochiaro PA (1996) Antagonists of integrin alpha v beta 3 inhibit retinal neovascularization in a murine model. Lab Invest 75:563-573.
20. Martin PL, Jiao Q, Cornacoff J, Hall W, Saville B, Nemeth JA, Schantz A, Mata M, Jang H, Fasanmade AA, et al. (2005) Absence of adverse effects in cynomolgus macaques treated with CNTO 95, a fully human anti-αv integrin monoclonal antibody, despite widespread tissue binding. Clin Cancer Res 11:6959-6965.
21. 3 (the vitronectin receptor). Drug Discov Today 5:397-408.
22. Mousa SA (2002) Anti-integrin as novel drug-discovery targets: potential therapeutic and diagnostic implications. Curr Opin Chem Biol 6:534-541.
23. Mousa SA (2003) αv vitronectin receptors in vascular-mediated disease. Med Res Rev 23:190-199.
24. 3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. J Clin Endocrinol Metab 90:2022-2028.
25. Patel N, Sun L, Moshinsky D, Chen H, Leahy K, Le P, Moss KG, Wang X, Rice A, Tam D, et al. (2003) A selective and oral small molecule inhibitor of vascular epithelial growth factor receptor (VEGFR)-2 and VEGFR-1 inhibits neovascularization and vascular permeability. J Pharmacol Exp Ther 306:838-845.
26. Ribatti D, Vacca A, Roncali L, and Dammacco F (2000) The chick embryo chorioallantoic membrane as a model for in vivo research on anti-angiogenesis. Curr Pharm Biotechnol 1:73-82.
27. Riecke B, Chavakis E, Bretzel RG, Linn T, Preissner KT, Brownlee M, and Hammes HP (2001) Topical application of integrin antagonists inhibit proliferative retinopathy. Horm Metab Res 33:307-311.
28. Rüegg C and Mariotti A (2003) Vascular integrins: pleiotropic adhesion and signaling molecules in vascular homeostasis and angiogenesis. Cell Mol Life Sci 60:1135-1157.
29. Simo R, Carrasco E, Garcia-Ramirez M, and Hernandez C (2006) Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. Curr Diabetes Rev 2:71-98.
30. Smith LE, Wesolowski E, McLellan A, Kostyk SK, D'Amato R, Sullivan R, and D'Amore PA (1994) Oxygen-induced retinopathy in the mouse. Invest Opthalmol Vis Sci 35:101-111.
31. Speicher MA, Danis RP, Criswell M, and Pratt L (2003) Pharmacologic therapy for diabetic retinopathy. Expert Opin Emerg Drugs 8:239-250.
32. Takagi H, Suzuma K, Otani A, Oh H, Koyama S, Ohashi H, Watanabe D, Ojima T, Suganami E, and Honda Y (2002) Role of vitronectin receptor-type integrins and osteopontin in ischemia-induced retinal neovascularization. Jpn J Ophthalmol 46:270-278.
33. 3 on vascular endothelial cells. J Cell Physiol 188:394-402.
34. Trikha M, Zhou Z, Nemeth JA, Chen Q, Sharp C, Emmell E, Giles-Komar J, and Nakada MT (2004) CNTO 95, a fully human monoclonal antibody that inhibits αv integrins, has antitumor and antiangiogenic activity in vivo. Int J Cancer 110:326-335.
35. Tsou R and Isik FF (2001) Integrin activation is required for VEGF and FGF receptor protein presence on human microvascular endothelial cells. Mol Cell Biochem 224:81-89.
36. Wilder RL (2002) Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases. Ann Rheum Dis 61:ii96 -ii99.
37. 5 integrins, reduces angiogenesis and VEGF expression in a mouse model of retinopathy of prematurity. Invest Ophthalmol Vis Sci 47:1600-1605.
38. Williams RAM, Baxter H, Forrester J, Kennedy-Martin T, and Girach A (2004) Epidemiology of diabetic retinopathy and madular oedema: a review. Eye 18:963-983.
39. Witmer AN, van Blijswijk BC, van Noorden CJF, Vrensen GFJM, and Schlingemann RO (2004) In vivo angiogenic phenotype of endothelial cells and pericytes induced by vascular endothelial growth factor-A. J Histochem Cytochem 52:39-52.
40. Xu Q, Quam T, and Adamis A (2001) Sensitive blood-retina barrier breakdown quantitation using Evans blue. Invest Ophthalmol Vis Sci 42:789-794.
41. Yasukawa T, Hoffmann S, Eichler W, Friedrichs U, Wang Y-S, and Wiedemann P (2004) Inhibition of experimental choroidal neovascularization in rats by an alphav-integrin antagonist. Curr Eye Res 28:359-366.
42. Yoon KC, Ahn KY, Lee JH, Chun BJ, Park SW, Seo MS, Park YG, and Kim KK (2005) Lipid-mediated delivery of brain-specific angiogenesis inhibitor 1 gene reduces corneal neovascularization in an in vivo rabbit model. Gene Ther 12:617-624.
43. Zarbin MA (2004) Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol 122:598-614.
44. Zhang D, Pier T, McNeel Douglas G, Wilding G, and Friedl A (2007) Effects of a monoclonal anti-αvβ3 integrin antibody on blood vessels - a pharmacodynamic study. Invest New Drugs 25:49-55.