A combinatorial in silico and cellular approach to identify a new class of compounds that target VEGFR2 receptor tyrosine kinase activity and angiogenesis

British Journal of Pharmacology

Volumn 166, Issue 2, 2012, Pages 737-748

  Kankanala, J ^a   Latham, A M ^a   Johnson, A P ^a   Homer Vanniasinkam, S ^b   Fishwick, C W G ^a   Ponnambalam, S ^a  

^a UNIVERSITY OF LEEDS   (United Kingdom)

^b LEEDS GENERAL INFIRMARY   (United Kingdom)

Author keywords

angiogenesis; endothelium; structure based design; tyrosine kinase inhibitor; VEGFR2

Indexed keywords

3,4 DIMETHOXY N (5 PHENYL 1H PYRAZOL 3 YL)BENZAMIDE; FIBROBLAST GROWTH FACTOR 2; FIBROBLAST GROWTH FACTOR RECEPTOR; JK P3; JK P5; N [4 (4 METHYLPIPERAZIN 1 YL)PHENYL] 1H INDAZOLE 3 CARBOXAMIDE; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG; VASCULOTROPIN A; VASCULOTROPIN RECEPTOR 2;

ANGIOGENESIS; ANTIANGIOGENIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; BINDING AFFINITY; CELL MIGRATION; CELL PROLIFERATION; COMPUTER MODEL; CONTROLLED STUDY; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG STRUCTURE; HUMAN; HUMAN CELL; IN VITRO STUDY; INTRACELLULAR SIGNALING; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; UMBILICAL VEIN ENDOTHELIAL CELL;

ANGIOGENESIS INHIBITORS; CELL PROLIFERATION; COMPUTER-AIDED DESIGN; DRUG DESIGN; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; NEOVASCULARIZATION, PHYSIOLOGIC; PROTEIN KINASE INHIBITORS; PYRAZOLES; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 1; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 3; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2; WOUND HEALING;

EID: 84859892839     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2011.01801.x     Document Type: Article

References (46)

1. Agarwal AK, Fishwick CW, (2010). Structure-based design of anti-infectives. Ann NY Acad Sci 1213: 20-45.
2. Ali MA, Bhogal N, Findlay JB, Fishwick CW, (2005). The first de novo-designed antagonists of the human NK(2) receptor. J Med Chem 48: 5655-5658. (Pubitemid 41298339)
3. Blanes MG, Oubaha M, Rautureau Y, Gratton JP, (2007). Phosphorylation of tyrosine 801 of vascular endothelial growth factor receptor-2 is necessary for Akt-dependent endothelial nitric-oxide synthase activation and nitric oxide release from endothelial cells. J Biol Chem 282: 10660-10669. (Pubitemid 47093458)
4. Boda K, Johnson AP, (2006). Molecular complexity analysis of de novo designed ligands. J Med Chem 49: 5869-5879. (Pubitemid 44484933)
5. Bracarda S, Caserta C, Sordini L, Rossi M, Hamzay A, Crino L, (2007). Protein kinase inhibitors in the treatment of renal cell carcinoma: sorafenib. Ann Oncol 18 (Suppl. 6): vi22-vi25.
6. Bruns AF, Herbert SP, Odell AF, Jopling HM, Hooper NM, Zachary IC, et al,. (2010). Ligand-stimulated VEGFR2 signaling is regulated by co-ordinated trafficking and proteolysis. Traffic 11: 161-174.
7. Carmeliet P, (2003). Angiogenesis in health and disease. Nat Med 9: 653-660. (Pubitemid 36749213)
8. Carmeliet P, (2005). VEGF as a key mediator of angiogenesis in cancer. Oncology 69 (Suppl. 3): 4-10. (Pubitemid 41680947)
9. Carmeliet P, Jain RK, (2011). Molecular mechanisms and clinical applications of angiogenesis. Nature 473: 298-307.
10. Cheng Y, Prusoff WH, (1973). Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22: 3099-3108.
11. Dinges J, Albert DH, Arnold LD, Ashworth KL, Akritopoulou-Zanze I, Bousquet PF, et al,. (2007). 1,4-Dihydroindeno[1,2-c]pyrazoles with acetylenic side chains as novel and potent multitargeted receptor tyrosine kinase inhibitors with low affinity for the hERG ion channel. J Med Chem 50: 2011-2029. (Pubitemid 46683055)
12. Ferrara N, Gerber HP, LeCouter J, (2003). The biology of VEGF and its receptors. Nat Med 9: 669-676. (Pubitemid 36749215)
13. Folkman J, (1971). Tumor angiogenesis: therapeutic implications. N Engl J Med 285: 1182-1186.
14. Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, et al,. (2004). Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 47: 1739-1749. (Pubitemid 38380917)
15. Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, et al,. (2006). Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 49: 6177-6196. (Pubitemid 44595196)
16. Halgren TA, Murphy RB, Friesner RA, Beard HS, Frye LL, Pollard WT, et al,. (2004). Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem 47: 1750-1759. (Pubitemid 38380918)
17. Hanahan D, Weinberg RA, (2011). Hallmarks of cancer: the next generation. Cell 144: 646-674.
18. Harris PA, Cheung M, Hunter RN, Brown ML, Veal JM, Nolte RT, et al,. (2005). Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. J Med Chem 48: 1610-1619. (Pubitemid 40364567)
19. Harris PA, Boloor A, Cheung M, Kumar R, Crosby RM, Davis-Ward RG, et al,. (2008). Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2- pyrimidinyl]amino]-2-m ethyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. J Med Chem 51: 4632-4640.
20. Hasinoff BB, Patel D, (2010). The lack of target specificity of small molecule anticancer kinase inhibitors is correlated with their ability to damage myocytes in vitro. Toxicol Appl Pharmacol 249: 132-139.
21. Holmes K, Roberts OL, Thomas AM, Cross MJ, (2007). Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition. Cell Signal 19: 2003-2012. (Pubitemid 47354167)
22. Howell GJ, Herbert SP, Smith JM, Mittar S, Ewan LC, Mohammed M, et al,. (2004). Endothelial cell confluence regulates Weibel-Palade body formation. Mol Membr Biol 21: 413-421. (Pubitemid 40030217)
23. Imrie H, Abbas A, Viswambharan H, Rajwani A, Cubbon RM, Gage M, et al,. (2009). Vascular insulin-like growth factor-I resistance and diet-induced obesity. Endocrinology 150: 4575-4582.
24. Jain RK, Duda DG, Clark JW, Loeffler JS, (2006). Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat Clin Pract Oncol 3: 24-40. (Pubitemid 43108832)
25. Knights V, Cook SJ, (2010). De-regulated FGF receptors as therapeutic targets in cancer. Pharmacol Ther 125: 105-117.
26. Koch S, Tugues S, Li X, Gualandi L, Claesson-Welsh L, (2011). Signal transduction by vascular endothelial growth factor receptors. Biochem J 437: 169-183.
27. Krystof V, Cankar P, Frysova I, Slouka J, Kontopidis G, Dzubak P, et al,. (2006). 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem 49: 6500-6509. (Pubitemid 44657444)
28. Latham AM, Molina-Paris C, Homer-Vanniasinkam S, Ponnambalam S, (2010). An integrative model for vascular endothelial growth factor A as a tumour biomarker. Integr Biol (Camb) 2: 397-407.
29. Latham AM, Bruns AF, Kankanala J, Johnson AP, Fishwick CW, Homer-Vanniasinkam S, et al,. (2012). Indolinones and anilinophthalazines differentially target VEGF-A and bFGF-mediated responses in primary human endothelial cells. Br J Pharmacol 165: 245-259.
30. Liu D, Jia H, Holmes DI, Stannard A, Zachary I, (2003). Vascular endothelial growth factor-regulated gene expression in endothelial cells: KDR-mediated induction of Egr3 and the related nuclear receptors Nur77, Nurr1, and Nor1. Arterioscler Thromb Vasc Biol 23: 2002-2007. (Pubitemid 37433192)
31. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, et al,. (2003). In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 9: 327-337. (Pubitemid 36109749)
32. Miyazaki Y, Matsunaga S, Tang J, Maeda Y, Nakano M, Philippe RJ, et al,. (2005). Novel 4-amino-furo[2,3-d]pyrimidines as Tie-2 and VEGFR2 dual inhibitors. Bioorg Med Chem Lett 15: 2203-2207. (Pubitemid 40523073)
33. Morphy R, (2010). Selectively nonselective kinase inhibition: striking the right balance. J Med Chem 53: 1413-1437.
34. Newman AC, Nakatsu MN, Chou W, Gershon PD, Hughes CC, (2011). The requirement for fibroblasts in angiogenesis: fibroblast-derived matrix proteins are essential for endothelial cell lumen formation. Mol Biol Cell 22: 3791-3800.
35. Noble ME, Endicott JA, Johnson LN, (2004). Protein kinase inhibitors: insights into drug design from structure. Science 303: 1800-1805. (Pubitemid 38374863)
36. Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L, (2006). VEGF receptor signalling-in control of vascular function. Nat Rev Mol Cell Biol 7: 359-371.
37. Richardson DR, Tran EH, Ponka P, (1995). The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents. Blood 86: 4295-4306.
38. Roskoski R, Jr, (2007). Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor. Biochem Biophys Res Commun 356: 323-328. (Pubitemid 46452568)
39. Schweighofer B, Testori J, Sturtzel C, Sattler S, Mayer H, Wagner O, et al,. (2009). The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation. Thromb Haemost 102: 544-554.
40. Takahashi T, Shibuya M, (1997). The 230 kDa mature form of KDR/Flk-1 (VEGF receptor-2) activates the PLC-gamma pathway and partially induces mitotic signals in NIH3T3 fibroblasts. Oncogene 14: 2079-2089. (Pubitemid 27237011)
41. Tille JC, Wood J, Mandriota SJ, Schnell C, Ferrari S, Mestan J, et al,. (2001). Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit. J Pharmacol Exp Ther 299: 1073-1085.
42. Usui T, Ban HS, Kawada J, Hirokawa T, Nakamura H, (2008). Discovery of indenopyrazoles as EGFR and VEGFR-2 tyrosine kinase inhibitors by in silico high-throughput screening. Bioorg Med Chem Lett 18: 285-288.
43. Wilhelm SM, Adnane L, Newell P, Villanueva A, Llovet JM, Lynch M, (2008). Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther 7: 3129-3140.
44. Zhang S, Cao Z, Tian H, Shen G, Ma Y, Xie H, et al,. (2011). SKLB1002, a novel potent inhibitor of vascular endothelial growth factor receptor 2 signaling, inhibits angiogenesis and tumor growth in vivo. Clin Cancer Res 17: 4439-4450.
45. Zhou T, Commodore L, Huang WS, Wang Y, Sawyer TK, Shakespeare WC, et al,. (2010). Structural analysis of DFG-in and DFG-out dual Src-Abl inhibitors sharing a common vinyl purine template. Chem Biol Drug Des 75: 18-28.
46. Zuccotto F, Ardini E, Casale E, Angiolini M, (2010). Through the 'gatekeeper door': exploiting the active kinase conformation. J Med Chem 53: 2681-2694.