Neuroprotective profile of novel Src kinase inhibitors in rodent models of cerebral ischemia

Journal of Pharmacology and Experimental Therapeutics

Volumn 331, Issue 3, 2009, Pages 827-835

  Liang, Shi ^a   Pong, Kevin ^a   Gonzales, Cathleen ^a   Chen, Yi ^a   Ling, Huai Ping ^a   Mark, Robert J ^a   Boschelli, Frank ^b   Boschelli, Diane H ^b   Ye, Fei ^b   Sosa, Ana Carolina Barrios ^b   Mansour, Tarek S ^b   Frost, Philip ^b   Wood, Andrew ^a   Pangalos, Menelas N ^a   Zaleska, Margaret M ^a  

^a PFIZER INC   (United States)

^b WYETH RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [(2,4 DICHLORO 5 METOXYPHENYL)AMINO] 6 METHOXY 7 [4 (4 METHYPIPERAZIN 1 YL)BUT 1 YNYL] 3 QUINOLINECARBONITRILE; BOSUTINIB; PROTEIN TYROSINE KINASE INHIBITOR; SKS 927; UNCLASSIFIED DRUG; 4 ((2,4 DICHLORO 5 METHOXYPHENYL)AMINO) 6 METHOXY 7 (4 (4 METHYPIPERAZIN 1 YL)BUT 1 YNYL) 3 QUINOLINECARBONITRILE; 4-((2,4-DICHLORO-5-METHOXYPHENYL)AMINO)-6-METHOXY-7-(4-(4-METHYPIPERAZIN-1-YL)BUT-1-YNYL)-3-QUINOLINECARBONITRILE; ANILINE DERIVATIVE; NEUROPROTECTIVE AGENT; NITRILE; PIPERAZINE DERIVATIVE; PROTEIN KINASE INHIBITOR; PROTEIN TYROSINE KINASE; QUINOLINE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BLOOD BRAIN BARRIER; BRAIN ISCHEMIA; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG EFFICACY; DRUG INHIBITION; DRUG STRUCTURE; IMMUNOHISTOCHEMISTRY; MIDDLE CEREBRAL ARTERY OCCLUSION; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; RAT; ANIMAL; BRAIN; CAPILLARY PERMEABILITY; CELL CULTURE; CHEMICAL STRUCTURE; CHEMISTRY; DISEASE MODEL; DOSE RESPONSE; DRUG ANTAGONISM; DRUG EFFECT; ENDOTHELIUM CELL; ENZYMOLOGY; FLOW CYTOMETRY; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; MALE; METABOLISM; NEUROPSYCHOLOGICAL TEST; THROMBOCYTE; TIME; WISTAR RAT;

ANILINE COMPOUNDS; ANIMALS; BLOOD PLATELETS; BRAIN; BRAIN ISCHEMIA; CAPILLARY PERMEABILITY; CELLS, CULTURED; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ENDOTHELIAL CELLS; FLOW CYTOMETRY; HUMANS; INJECTIONS, INTRAVENOUS; MALE; MOLECULAR STRUCTURE; NEUROPROTECTIVE AGENTS; NEUROPSYCHOLOGICAL TESTS; NITRILES; PIPERAZINES; PROTEIN KINASE INHIBITORS; QUINOLINES; RATS; RATS, WISTAR; SRC-FAMILY KINASES; TIME FACTORS;

EID: 73349110106     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.109.156562     Document Type: Article

References (41)

1. Abu-Ghazaleh R, Kabir J, Jia H, Lobo M, and Zachary I (2001) Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells. Biochem J 360:255-264.
2. Bantscheff M, Eberhard D, Abraham Y, Bastuck S, Boesche M, Hobson S, Mathieson T, Perrin J, Raida M, Rau C, et al. (2007) Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors. Nat Biotechnol 25:1035-1044.
3. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, and Bartkowski H (1986) Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 17:472-476.
4. Belayev L, Busto R, Zhao W, and Ginsberg MD (1996) Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats. Brain Res 739:88-96.
5. Boschelli DH, Barrios Sosa AC, Golas JM, and Boschelli F (2007) Inhibition of Src kinase activity by 7-ethynyl-4-phenylamino-3- quinolinecarbonitriles: identification of SKS-927. Bioorg Med Chem Lett 17:1358-1361.
6. Boschelli DH and Boschelli F (2007) Bosutinib (SKI-606). Drugs Future 32:481.
7. Boschelli DH, Ye F, Wang YD, Dutia M, Johnson SL, Wu B, Miller K, Powell DW, Yaczko D, Young M, et al. (2001) Optimization of 4-phenylamino-3- quinolinecarbonitriles as potent inhibitors of Src kinase activity. J Med Chem 44:3965-3977.
8. Brillault J, Berezowski V, Cecchelli R, and Dehouck MP (2002) Intercommunications between brain capillary endothelial cells and glial cells increase the transcellular permeability of the blood-brain barrier during ischaemia. J Neurochem 83:807-817.
9. Cataldi M, Taglialatela M, Guerriero S, Amoroso S, Lombardi G, di Renzo G, and Annunziato L (1996) Protein-tyrosine kinases activate while protein-tyrosine phosphatases inhibit L-type calcium channel activity in pituitary GH3 cells. J Biol Chem 271:9441-9446.
10. Chen ST, Hsu CY, Hogan EL, Maricq H, and Balentine JD (1986) A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction. Stroke 17:738-743.
11. Croll SD and Wiegand SJ (2001) Vascular growth factors in cerebral ischemia. Mol Neurobiol 23:121-135.
12. De Ryck M, Van Reempts J, Borgers M, Wauquier A, and Janssen PA (1989) Photochemical stroke model: flunarizine prevents sensorimotor deficits after neocortical infarcts in rats. Stroke 20:1383-1390.
13. Donnan GA, Fisher M, Macleod M, and Davis SM (2008) Stroke. Lancet 371:1612-1623.
14. Eliceiri BP, Paul R, Schwartzberg PL, Hood JD, Leng J, and Cheresh DA (1999) Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Mol Cell 4:915-924.
15. 5 in vascular endothelial growth factor signaling. J Cell Biol 157:149-160.
16. Fadool DA, Holmes TC, Berman K, Dagan D, and Levitan IB (1997) Tyrosine phosphorylation modulates current amplitude and kinetics of a neuronal voltage-gated potassium channel. J Neurophysiol 78:1563-1573.
17. Feuerstein GZ, Zaleska MM, Krams M, Wang X, Day M, Rutkowski JL, Finklestein SP, Pangalos MN, Poole M, Stiles GL, et al. (2008) Missing steps in the STAIR case: a Translational Medicine perspective on the development of NXY-059 for treatment of acute ischemic stroke. J Cereb Blood Flow Metab 28:217-219.
18. Guo J, Wu HW, Hu G, Han X, De W, and Sun YJ (2006) Sustained activation of Src-family tyrosine kinases by ischemia: a potential mechanism mediating extracellular signal-regulated kinase cascades in hippocampal dentate gyrus. Neuroscience 143:827-836.
19. Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, et al. (2008) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 359:1317-1329.
20. Issa R, Krupinski J, Bujny T, Kumar S, Kaluza J, and Kumar P (1999) Vascular endothelial growth factor and its receptor, KDR, in human brain tissue after ischemic stroke. Lab Invest 79:417-425.
21. Kimura R, Nakase H, Tamaki R, and Sakaki T (2005) Vascular endothelial growth factor antagonist reduces brain edema formation and venous infarction. Stroke 36:1259-1263.
22. Lennmyr F, Ericsson A, Gerwins P, Akterin S, Ahlström H, and Terént A (2004) Src family kinase-inhibitor PP2 reduces focal ischemic brain injury. Acta Neurol Scand 110:175-179.
23. Longa EZ, Weinstein PR, Carlson S, and Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84-91.
24. Mukaiyama H, Nishimura T, Shiohara H, Kobayashi S, Komatsu Y, Kikuchi S, Tsuji E, Kamada N, Ohnota H, and Kusama H (2007) Discovery of novel 2-anilinopyrazolo[1,5-α]pyrimidine derivatives as c-Src kinase inhibitors for the treatment of acute ischemic stroke. Chem Pharm Bull (Tokyo) 55:881-889.
25. O'Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, and Howells DW (2006) 1,026 experimental treatments in acute stroke. Ann Neurol 59:467-477.
26. Paul R, Zhang ZG, Eliceiri BP, Jiang Q, Boccia AD, Zhang RL, Chopp M, and Cheresh DA (2001) Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke. Nat Med 7:222-227.
27. Plate KH, Beck H, Danner S, Allegrini PR, and Wiessner C (1999) Cell type specific upregulation of vascular endothelial growth factor in an MCA-occlusion model of cerebral infarct. J Neuropathol Exp Neurol 58:654-666.
28. + neoplastic cells. Cancer Res 66:11314-11322.
29. Remsing Rix LL, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Müller A, Baumgartner C, Valent P, Augustin M, et al. (2009) Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia 23:477-485.
30. Salter MW and Kalia LV (2004) Src kinases: a hub for NMDA receptor regulation. Nat Rev Neurosci 5:317-328.
31. Savitz SI and Fisher M (2007) Future of neuroprotection for acute stroke: in the aftermath of the SAINT trials. Ann Neurol 61:396-402.
32. Sun G, Sharma AK, and Budde RJ (1998) Autophosphorylation of Src and Yes blocks their inactivation by Csk phosphorylation. Oncogene 17:1587-1595.
33. Thomas SM and Brugge JS (1997) Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol 13:513-609.
34. van Bruggen N, Thibodeaux H, Palmer JT, Lee WP, Fu L, Cairns B, Tumas D, Gerlai R, Williams SP, van Lookeren Campagne M, et al. (1999) VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain. J Clin Invest 104:1613-1620.
35. Weis S, Cui J, Barnes L, and Cheresh D (2004a) Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis. J Cell Biol 167:223-229.
36. Weis S, Shintani S, Weber A, Kirchmair R, Wood M, Cravens A, McSharry H, Iwakura A, Yoon YS, Himes N, et al. (2004b) Src blockade stabilizes a Flk/cadherin complex, reducing edema and tissue injury following myocardial infarction. J Clin Invest 113:885-894.
37. Weis SM and Cheresh DA (2005) Pathophysiological consequences of VEGF-induced vascular permeability. Nature 437:497-504.
38. Zaleska MM, Mercado ML, Chavez J, Feuerstein GZ, Pangalos MN, and Wood A (2009) The development of stroke therapeutics: promising mechanisms and translational challenges. Neuropharmacology 56:329-341.
39. Zalewska T, Ziemka-Nałecz M, and Domañska-Janik K (2005) Transient forebrain ischemia effects interaction of Src, FAK, and PYK2 with the NR2B subunit of N-methyl-D-aspartate receptor in gerbil hippocampus. Brain Res 1042:214-223.
40. Zhang Z and Chopp M (2002) Vascular endothelial growth factor and angiopoietins in focal cerebral ischemia. Trends Cardiovasc Med 12:62-66.
41. Zhang ZG, Zhang L, Jiang Q, Zhang R, Davies K, Powers C, Bruggen N, and Chopp M (2000) VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain. J Clin Invest 106:829-838.