Discovery of Novel Vascular Endothelial Growth Factor Receptor 2 Inhibitors: A Virtual Screening Approach

Chemical Biology and Drug Design

Volumn 80, Issue 6, 2012, Pages 893-901

  Zhang, Lei ^a   Wang, Xuejian ^a   Feng, Jinhong ^b   Jia, Yuping ^c   Xu, Fuming ^a   Xu, Wenfang ^a  

^a SHANDONG UNIVERSITY   (China)

^b QILU UNIVERSITY OF TECHNOLOGY   (China)

^c Shandong Institute of Pharmaceutical Industry   (China)

Author keywords

Molecular dynamic simulation; Vascular endothelial growth factor receptor 2 inhibitors; Virtual screening

Indexed keywords

1 NAPHTHOL; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; FUNCTIONAL GROUP; RECEPTOR BLOCKING AGENT; SORAFENIB; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 2 INHIBITOR;

ANIMAL TISSUE; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; CELL PROLIFERATION; CONTROLLED STUDY; DATA BASE; DRUG EFFICACY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SCREENING; HUMAN; HUMAN CELL; HYDROPHOBICITY; IN VITRO STUDY; LIGAND BINDING; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; MOLECULAR MODEL; MOUSE; NONHUMAN; PHARMACOPHORE; PRIORITY JOURNAL; SIMULATION;

ANGIOGENESIS INHIBITORS; ANIMALS; BINDING SITES; CELL LINE; CELL PROLIFERATION; DATABASES, FACTUAL; DRUG EVALUATION, PRECLINICAL; HCT116 CELLS; HELA CELLS; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; K562 CELLS; MICE; MOLECULAR DOCKING SIMULATION; PROTEIN KINASE INHIBITORS; PROTEIN STRUCTURE, TERTIARY; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 84868012272     PISSN: 17470277     EISSN: 17470285     Source Type: Journal    
DOI: 10.1111/cbdd.12036     Document Type: Article

References (21)

1. Brunelleschi S., Penengo L., Santoro M.M., Gaudino G. (2002) Receptor tyrosine kinases as target for anti-cancer therapy. Curr Pharm Des;8:1959-1972.
2. Ferrara N., Gerber H.P., LeCouter J. (2003) The biology of VEGF and its receptors. Nat Med;9:669-676.
3. Olsson A.K., Dimberg A., Kreuger J., Claesson-Welsh L. (2006) VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol;7:359-371.
4. Zhang R., Xu Y.Q., Ekman N., Wu Z.H., Wu J., Alitalo K., Min W. (2003) Etk/Bmx transactivates vascular endothelial growth factor 2 and recruits phosphatidylinositol 3-kinase to mediate the tumor necrosis factor-induced angiogenic pathway. J Biol Chem;278:51267-51276.
5. Masson-Gadais B., Houle F., Laferriere J., Huot J. (2003) Integrin alpha(v)beta(3) requirement for VEGFR2-mediated activation of SAPK2/p38 and for Hsp90-dependent phosphorylation of focal adhesion kinase in endothelial cells activated by VEGF. Cell Stress Chaperones;8:37-52.
6. Kurzrock R., Sherman S., Hong D., Ng C., Frye J., Janisch L., Ratain M.J., Salgia R. (2008) A phase I study of XL184, a MET, VEGFR2, and RET kinase inhibitor, administered orally to patients (pts) with advanced malignancies, including a subgroup of pts with medullary thyroid cancer (MTC). EJC Suppl;6:119-119.
7. Marathe P.H., Kamath A.V., Zhang Y.P., D'Arienzo C., Bhide R., Fargnoli J. (2009) Preclinical pharmacokinetics and in vitro metabolism of brivanib (BMS-540215), a potent VEGFR2 inhibitor and its alanine ester prodrug brivanib alaninate. Cancer Chemother Pharmacol;65:55-66.
8. Marathe P., Tang Y.W., Sleczka B., Rodrigues D., Gavai A., Wong T., Christopher L., Zhang H.J. (2010) Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci;99:3579-3593.
9. Yi T., Yi Z., Cho S.G., Luo J., Pandey M.K., Aggarwal B.B., Liu M. (2008) Gambogic acid inhibits angiogenesis and prostate tumor growth by suppressing vascular endothelial growth factor receptor 2 signaling. Cancer Res;68:1843-1850.
10. Wilhelm S.M., Carter C., Tang L.Y., Wilkie D., McNabola A., Rong H., Chen C. et al. (2004) BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res;64:7099-7109.
11. Lee K., Jeong K.-W., Lee Y., Song J.Y., Kim M.S., Lee G.S., Kim Y. (2010) Pharmacophore modeling and virtual screening studies for new VEGFR-2 kinase inhibitors. Eur J Med Chem;45:5420-5427.
12. Potashman M.H., Bready J., Coxon A., DeMelfi T.M., DiPietro L., Doerr N., Elbaum D. et al. (2007) Design, synthesis, and evaluation of orally active Benzimidazoles and Benzoxazoles as vascular endothelial growth factor-2 receptor tyrosine kinase inhibitors. J Med Chem;50:4351-4373.
13. Fiser A., Do R.K.G., Sali A. (2000) Modeling of loops in protein structures. Protein Sci;9:1753-1773.
14. Jain A.N. (2003) Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine. J Med Chem;46:499-511.
15. Jain A.N. (2007) Surflex-Dock 2.1: robust performance from ligand energetic modeling, ring flexibility, and knowledge-based search. J Comput Aided Mol Des;21:281-306.
16. Berendsen H.J.C., van der Spoel D., van Drunen R. (1995) GROMACS: a message-passing parallel molecular dynamics implementation. Comput Phys Commun;91:43-56.
17. Lindahl E., Hess B., van der Spoel D. (2001) GROMACS 3.0: a package for molecular simulation and trajectory analysis. J Mol Model;7:306-317.
18. Van der Spoel D., Lindahl E., Hess B., Groenhof G., Mark A.E., Berendsen H.J.C. (2005) GROMACS: fast, flexible, and free. J Comput Chem;26:1701-1718.
19. Darden T., York D., Pedersen L. (1993) Particle mesh Ewald: an N·log(N) method for Ewald sums in large systems. J Chem Phys;98:10089-10092.
20. Pettersen E.F., Goddard T.D., Huang C.C., Couch G.S., Greenblatt D.M., Meng E.C., Ferrin T.E. (2004) UCSF chimera - a visualization system for exploratory research and analysis. J Comput Chem;25:1605-1612.
21. Wallace A.C., Laskowski R.A., Thornton J.M. (1995) LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng;8:127-134.