Molecular modeling studies of vascular endothelial growth factor receptor tyrosine kinase inhibitors using QSAR and docking

Journal of Molecular Graphics and Modelling

Volumn 27, Issue 5, 2009, Pages 642-654

  Du, Juan ^a   Lei, Beilei ^a   Qin, Jin ^a   Liu, Huanxiang ^a   Yao, Xiaojun ^a  

^a LANZHOU UNIVERSITY   (China)

Author keywords

CoMFA; CoMSIA; Docking; KDR inhibitor; Vascular endothelial growth factor receptor 2 (VEGFR 2)

Indexed keywords

AGENTS; ALIGNMENT; AMINO ACIDS; BINDING ENERGY; BIOACTIVITY; DOCKING; ENZYME INHIBITION; GROWTH (MATERIALS); MOLECULAR GRAPHICS; MOLECULAR MODELING; PEPTIDES; SELF ASSEMBLY;

3D-QSAR; ANTI CANCER AGENTS; BINDING MODES; BIOACTIVE CONFORMATIONS; COMFA; COMPARATIVE MOLECULAR FIELD ANALYSES; COMSIA; KDR INHIBITOR; KINASE INSERT DOMAINS; MOLECULAR MODELING STUDIES; MOLECULAR SIMILARITIES; RECEPTOR TYROSINE KINASES; SELECTIVE INHIBITORS; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 2 (VEGFR-2); VASCULAR ENDOTHELIAL GROWTH FACTORS;

THREE DIMENSIONAL;

PROTEIN TYROSINE KINASE INHIBITOR; VASCULOTROPIN RECEPTOR;

ARTICLE; BINDING SITE; CHEMICAL STRUCTURE; COMPARATIVE MOLECULAR FIELD ANALYSIS; COMPARATIVE MOLECULAR SIMILARITY INDICES ANALYSIS; HYDROGEN BOND; HYDROPHOBICITY; MOLECULAR DOCKING; MOLECULAR MODEL; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

ANTINEOPLASTIC AGENTS; COMPUTER SIMULATION; DRUG DESIGN; HUMANS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN KINASE INHIBITORS; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 57649229413     PISSN: 10933263     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmgm.2008.10.006     Document Type: Article

References (43)

1. Risau W. Mechanisms of angiogenesis. Nature 386 (1997) 671-674
2. Ribatti D., Vacca A., Nico B., Roncali L., and Dammacco F. Postnatal vasculogenesis. Mech. Dev. 100 (2001) 157-163
3. Fava G.A. Affective disorders and endocrine disease. New insights from psychosomatic studies. Psychosomatics 35 (1994) 341-353
4. Walsh D.A., and Haywood L. Angiogenesis: a therapeutic target in arthritis. Curr. Opin. Invest. Drugs 2 (2001) 1054-1063
5. Aiello L.P., Avery R.L., Arrigg P.G., Keyt B.A., Jampel H.D., Shah S.T., Pasquale L.R., Thieme H., Iwamoto M.A., Park J.E., Nguyen H.V., Aiello L.M., Ferrara N., and King G.L. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N. Engl. J. Med. 331 (1994) 1480-1487
6. Detmar M. The role of VEGF and thrombospondins in skin angiogenesis. J. Dermatol. Sci. 24 (2000) 78-84
7. Folkman J. Anti-angiogenesis: new concept for therapy of solid tumors. Ann. Surg. 175 (1972) 409-416
8. Liotta L.A., Steeg P.S., and Stetler-Stevenson W.G. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64 (1991) 327-336
9. Shawver L.K., Lipson K.E., Fong T.A.T., McMahon G., Plowman G.D., and Strawn L.M. Receptor tyrosine kinases as targets for inhibition of angiogenesis. Drug Discov. Today 2 (1997) 50-63
10. Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat. Rev. Cancer 2 (2002) 795-803
11. Carmeliet P., and Jain R.K. Angiogenesis in cancer and other diseases. Nature 407 (2000) 249-257
12. Baka S., Clamp A.R., and Jayson G.C. A review of the latest clinical compounds to inhibit VEGF in pathological angiogenesis. Expert Opin. Ther. Targets 10 (2006) 867-876
13. Sepp-Lorenzino L., and Thomas K.A. Antiangiogenic agents targeting vascular endothelial growth factor and its receptors in clinical development. Expert Opin. Invest. Drugs 11 (2002) 1447-1465
14. Klebl B.M., and Müller G. Second-generation kinase inhibitors. Expert Opin. Ther. Targets 9 (2005) 975-993
15. Supuran C.T., and Scozzafava A. Protein tyrosine kinase inhibitors as anticancer agents. Expert Opin. Ther. Pat. 14 (2004) 35-53
16. Holmes K., Roberts O.L., Thomas A.M., and Cross M.J. Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition. Cell. Signal. 19 (2007) 2003-2012
17. Ferrara N., Hillan K.J., Gerber H.P., and Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat. Rev. Drug Discov. 3 (2004) 391-400
18. Sakamoto K.M. Su-11248 Sugen. Curr. Opin. Invest. Drugs 5 (2004) 1329-1339
19. Thomas A.L., Morgan B., Dreves J., Unger C., Wiedenmann B., Vanhoefer U., Laurent D., Dugan M., and Steward W.P. Vascular endothelial growth factor receptor tyrosine kinase inhibitors: PTK787/ZK 222584. Semin. Oncol. 30 (2003) 32-38
20. Ahman T., and Eisen T. Kinase Inhibition with BAY 43-9006 in renal cell carcinoma. Clin. Cancer Res. 10 (2004) 6388-6392
21. Ruggeri B., Singh J., Gingrich D., Angeles T., Albom M., Yang S., Chang H., Robinson C., Hunter K., Dobrzanski P., Jones-Bolin S., Pritchard S., Aimone L., Klein-Szanto A., Herbert J.M., Bono F., Schaeffer P., Casellas P., Bourie B., Pili R., Isaacs J., Ator M., Hudkins R., Vaught J., Mallamo J., and Dionne C. CEP-7055: a novel, orally active pan inhibitor of vascular endothelial growth factor receptor tyrosine kinases with potent antiangiogenic activity and antitumor efficacy in preclinical models. Cancer Res. 63 (2003) 5978-5991
22. Beebe J.S., Jani J.P., Knauth E., Goodwin P., Higdon C., Rossi A.M., Emerson E., Finkelstein M., Floyd E., Harriman S., Atherton J., Hillerman S., Soderstrom C., Kou K., Gant T., Noe M.C., Foster B., Rastinejad F., Marx M.A., Schaeffer T., Whalen P.M., and Roberts W.G. Pharmacological characterization of CP-547,632, a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for cancer therapy. Cancer Res. 63 (2003) 7301-7309
23. Ryan A.J., and Wedge S.R. ZD6474-a novel inhibitor of VEGFR and EGFR tyrosine kinase activity. Br. J. Cancer 92 (2005) 6-13
24. Polverino A., Coxon A., Starnes C., Diaz Z., DeMelfi T., Wang L., Bready J., Estrada J., Cattley R., Kaufman S., Chen D., Gan Y., Kumar G., Meyer J., Neervannan S., Alva G., Talvenheimo J., Montestruque S., Tasker A., Patel V., Radinsky R., and Kendall R. AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts. Cancer Res. 66 (2006) 8715-8721
25. Wissner A., Floyd M.B., Johnson B.D., Fraser H., Ingalls C., Nittoli T., Dushin R.G., Discafani C., Nilakantan R., Marini J., Ravi M., Cheung K., Tan X., Musto S., Annable T., Siegel M.M., and Loganzo F. 2-(Quinazolin-4-ylamino)-[1,4]benzoquinones as covalent-binding, irreversible inhibitors of the kinase domain of vascular endothelial growth factor receptor-2. J. Med. Chem. 48 (2005) 7560-7581
26. Bhide R.S., Cai Z.W., Zhang Y.Z., Qian L., Wei D., Barbosa S., Lombardo L.J., Borzilleri R.M., Zheng X., Wu L.I., Barrish J.C., Kim S.H., Leavitt K., Mathur A., Leith L., Chao S., Wautlet B., Mortillo S., Jeyaseelan R., Kukral D., Hunt J.T., Kamath A., Fura A., Vyas V., Marathe P., D'Arienzo C., Derbin G., and Fargnoli J. Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor. J. Med. Chem. 49 (2006) 2143-2146
27. Borzilleri R.M., Bhide R.S., Barrish J.C., D'Arienzo C.J., Derbin G.M., Fargnoli J., Hunt J.T., Jeyaseelan R., Kamath A., Kukral D.W., Marathe P., Mortillo S., Qian L., Tokarski J.S., Wautlet B.S., Zheng X., and Lombardo L.J. Discovery and evaluation of N-cyclopropyl-2,4-difluoro-5-((2-(pyridin-2-ylamino)thiazol-5-ylmethyl)amino)benzamide (BMS-605541), a selective and orally efficacious inhibitor of vascular endothelial growth factor receptor-2. J. Med. Chem. 49 (2006) 3766-3769
28. Potashman M.H., Bready J., Coxon A., DeMelfi T.M., DiPietro L., Doerr N., Elbaum D., Estrada J., Gallant P., Germain J., Gu Y., Harmange J.C., Kaufman S.A., Kendall R., Kim J.L., Kumar G.N., Long A.M., Neervannan S., Patel V.F., Polverino A., Rose P., vanderPlas S., Whittington D., Zanon R., and Zhao H. Design, synthesis, and evaluation of orally active benzimidazoles and benzoxazoles as vascular endothelial growth factor-2 receptor tyrosine kinase inhibitors. J. Med. Chem. 50 (2007) 4351-4373
29. Hasegawa M., Nishigaki N., Washio Y., Kano K., Harris P.A., Sato H., Mori I., West R.I., Shibahara M., Toyoda H., Wang L., Nolte R.T., Veal J.M., and Cheung M. Discovery of novel benzimidazoles as potent inhibitors of TIE-2 and VEGFR-2 tyrosine kinase receptors. J. Med. Chem. 50 (2007) 4453-4470
30. Cai Z.-w., Wei D., Borzilleri R.M., Qian L., Kamath A., Mortillo S., Wautlet B., Henley B.J., Jeyaseelan Sr. R., Tokarski J., Hunt J.T., Bhide R.S., Fargnoli J., and Lombardo L.J. Synthesis, SAR, and evaluation of 4-[2,4-difluoro-5-(cyclopropylcarbamoyl)phenylamino]pyrrolo[2,1-f][1,2,4]triazine-based VEGFR-2 kinase inhibitors. Bioorg. Med. Chem. Lett. 18 (2008) 1354-1358
31. Ilovich O., Jacobson O., Aviv Y., Litchi A., Chisin R., and Mishani E. Formation of fluorine-18 labeled diaryl ureas-labeled VEGFR-2/PDGFR dual inhibitors as molecular imaging agents for angiogenesis. Bioorg. Med. Chem. 16 (2008) 4242-4251
32. Ruel R., Thibeault C., L'Heureux A., Martel A., Cai Z.-W., Wei D., Qian L., Barrish J.C., Mathur A., D'Arienzo C., Hunt J.T., Kamath A., Marathe P., Zhang Y., Derbin G., Wautlet B., Mortillo S., Jeyaseelan Sr. R., Henley B., Tejwani R., Bhide R.S., Trainor G.L., Fargnoli J., and Lombardo L.J. Discovery and preclinical studies of 5-isopropyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (BMS-645737), an in vivo active potent VEGFR-2 inhibitor. Bioorg. Med. Chem. Lett. 18 (2008) 2985-2989
33. Harmange J.-C., Weiss M.M., Germain J., Polverino A.J., Borg G., Bready J., Chen D., Choquette D., Coxon A., DeMelfi T., DiPietro L., Doerr N., Estrada J., Flynn J., Graceffa R.F., Harriman P., Kaufman S., La D.S., Long A., Martin M.W., Neervannan S., Patel V.F., Potashman M., Regal K., Roveto P.M., Schrag M.L., Starnes C., Tasker A., Teffera Y., Wang L., White R.D., Whittington D.A., and Zanon R. Naphthamides as novel and potent vascular endothelial growth factor receptor tyrosine kinase inhibitors: design, synthesis, and evaluation. J. Med. Chem. 51 (2008) 1649-1667
34. Weiss M.M., Harmange J.-C., Polverino A.J., Bauer D., Berry L., Berry V., Borg G., Bready J., Chen D., Choquette D., Coxon A., DeMelfi T., Doerr N., Estrada J., Flynn J., Graceffa R.F., Harriman S.P., Kaufman S., La D.S., Long A., Neervannan S., Patel V.F., Potashman M., Regal K., Roveto P.M., Schrag M.L., Starnes C., Tasker A., Teffera Y., Whittington D.A., and Zanon R. Evaluation of a series of naphthamides as potent, orally active vascular endothelial growth factor receptor-2 tyrosine kinase inhibitors. J. Med. Chem. 51 (2008) 1668-1680
35. La D.S., Belzile J., Bready J.V., Coxon A., DeMelfi T., Doerr N., Estrada J., Flynn J.C., Flynn S.R., Graceffa R.F., Harriman S.P., Larrow J.F., Long A.M., Martin M.W., Morrison M.J., Patel V.F., Roveto P.M., Wang L., Weiss M.M., Whittington D.A., Teffera Y., Zhao Z., Polverino A.J., and Harmange J.-C. Novel 2,3-dihydro-1,4-benzoxazines as potent and orally bioavailable inhibitors of tumor-driven angiogenesis. J. Med. Chem. 51 (2008) 1695-1705
36. Cramer III R.D., Patterson D.E., and Bunce J.D. Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J. Am. Chem. Soc. 110 (1988) 5959-5967
37. Cramer III R.D., Bunce J.D., and Patterson D.E. Crossvalidation, bootstrapping, and partial least squares compared with multiple regression in conventional QSAR studies. Quant. Struct.-Act. Relat. 7 (1988) 18-25
38. Klebe G., Abraham U., and Mietzner T. Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity. J. Med. Chem. 37 (1994) 4130-4146
39. Sybyl version6.9, Tripos Associates, St. Louis, MO, 1999.
40. Rarey M., Kramer B., Lengauer T., and Klebe G. A fast flexible docking method using an incremental construction algorithm. J. Mol. Biol. 261 (1996) 470-489
41. Stahle L., and Wold S. Multivariate data analysis and experimental design in biomedical research. Prog. Med. Chem. 25 (1988) 292-338
42. W.L. DeLano, The PyMOL Molecular Graphics System DeLano Scientific, Palo Alto, CA, USA, 2002.
43. Wallace A.C., Laskowski R.A., and Thornton J.M. LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions. Prot. Eng. 8 (1995) 127-134