Exploring novel KDR inhibitors based on pharmaco-informatics methodology

References

• Ferrara , N. 2001 . Role of vascular endothelial growth factor in regulation of physiological angiogenesis . Am. J. Physiol. Cell Physiol. , 280 : C1358 – C1366 .
   PubMed Web of Science ®Google Scholar
• Pugh , C.W. and Ratcliffe , P.J. 2003 . Regulation of angiogenesis by hypoxia: Role of the HIF system . Nature Med. , 9 : 677 – 684 .
   PubMed Web of Science ®Google Scholar
• Ferrara , N. 1999 . Role of vascular endothelial growth factor in the regulation of angiogenesis . Kidney Intern. , 56 : 794 – 814 .
   PubMed Web of Science ®Google Scholar
• Carmeliet , P. and Jain , R.K. 2000 . Angiogenesis in cancer and other diseases . Nature , 407 : 249 – 257 .
   PubMed Web of Science ®Google Scholar
• Schneider , B.P. and Miller , K.D. 2005 . Angiogenesis of breast cancer . J. Clin. Oncol. , 23 : 1782 – 1790 .
   PubMed Web of Science ®Google Scholar
• Khurana , R. , Simons , M. , Martin , J.F. and Zachary , I.C. 2005 . Role of angiogenesis in cardiovascular disease: A critical appraisal . Circulation , 112 : 1813 – 1824 .
   PubMed Web of Science ®Google Scholar
• Lee , J.S. , Semela , D. , Iredale , J. and Shah , V.H. 2007 . Sinusoidal remodeling and angiogenesis: A new function for the liver-specific pericyte? . Hepatology , 45 : 817 – 825 .
   PubMed Web of Science ®Google Scholar
• Kirka , S. , Frank , J.A. and Karlik , S. 2004 . Angiogenesis in multiple sclerosis: is it good, bad or an epiphenomenon? . J. Neurol. Sci. , 217 : 125 – 130 .
   PubMedGoogle Scholar
• Koutroubakis , I.E. , Tsiolakidou , G. , Karmiris , K. and Kouroumalis , E.A. 2006 . Role of angiogenesis in inflammatory bowel disease . Inflamm. Bowel Dis. , 12 : 515 – 523 .
   PubMed Web of Science ®Google Scholar
• Paleolog , E.M. and Fava , R.A. 1998 . Angiogenesis in rheumatoid arthritis: implications for future therapeutic strategies . Springer Semin. Immunopathol. , 20 : 73 – 94 .
   PubMedGoogle Scholar
• Clapp , C. , Thebault , S. , Jeziorski , M.C. and Escalera , G.M. 2009 . Peptide hormone regulation of angiogenesis . Physiol. Rev. , 89 : 1177 – 1215 .
   PubMed Web of Science ®Google Scholar
• Carmeliet , P. 2005 . VEGF as a key mediator of angiogenesis in cancer . Oncology , 69 : 4 – 10 .
   PubMed Web of Science ®Google Scholar
• Tournaire , R.B. , Demange , C. , Malavaud , B. , Vassy , R. , Rouyre , S. , Kraemer , M. , Plouret , J. , Derbin , C. , Perret , G. and Mazie , J.C. 2000 . Identification of a peptide blocking vascular endothelial growth factor (VEGF)-mediated angiogenesis . EMBO J. , 19 : 1525 – 33 .
   PubMedGoogle Scholar
• Joukov , V. , Pajusola , K. , Kaipainen , A. , Chilov , D. , Lahtinen , I. , Kukk , E. , Saksela , O. , Kalkkinen , N. and Alitalo , K. 1996 . A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases . EMBO J. , 15 : 290 – 298 .
   PubMed Web of Science ®Google Scholar
• Hanrahan , V. , Currie , M.J. , Gunningham , S.P. , Morrin , H.R. , Scott , P.A. , Robinson , B.A. and Fox , S.B. 2003 . The angiogenic switch for vascular endothelial growth factor (VEGF)-A, VEGF-B, VEGF-C, and VEGF-D in the adenoma–carcinoma sequence during colorectal cancer progression . J. Pathol. , 200 : 183 – 194 .
   PubMed Web of Science ®Google Scholar
• Joukov , V. , Sorsa , T. , Kumar , V. , Jelrsch , M. , Welsh , L.C. , Cao , Y. , Saksela , O. , Kalkkinen , N. and Alitalo , K. 1997 . Proteolytic processing regulates receptor specificity and activity of VEGF-C . EMBO J. , 16 : 3898 – 3911 .
   PubMed Web of Science ®Google Scholar
• Ellis , L.M. and Hicklin , D.J. 2008 . VEGF-targeted therapy: mechanisms of anti-tumour activity . Nature Rev. , 8 : 579 – 591 .
   Google Scholar
• Kendall , R.L. , Rutledge , R.Z. , Mao , X. , Tebben , A.J. , Hungate , R.W. and Thomas , K.A. 1999 . Vascular endothelial growth factor receptor KDR tyrosine kinase activity is increased by autophosphorylation of two activation loop tyrosine residues . J. Biol. Chem. , 274 : 6453 – 6460 .
   PubMed Web of Science ®Google Scholar
• Antonescu , C.R. , Yoshida , A. and Guo , T. 2009 . KDR activating mutations in human angiosarcomas are sensitive to specific kinase inhibitors . Cancer Res. , 69 : 7175 – 7179 .
   PubMed Web of Science ®Google Scholar
• Pander , J. , Gelderblom , H. and Guchelaar , H. 2007 . Pharmacogenetics of EGFR and VEGF inhibition . Drug Discov. Today , 12 : 1054 – 1060 .
   PubMed Web of Science ®Google Scholar
• X.J. Ma, S. Dahiya, E. Richardson, M. Erlander, and D. C. Sgroi, Gene expression profiling of the tumor microenvironment during breast cancer progression, Breast Cancer Res. 11 (2009):R7.
   Google Scholar
• Huang , Y. , Reyniès , A. , Leval , L. , Ghazi , B. , Garcia , N. , Travert , M. , Bosq , J. , Brière , J. , Petit , B. , Thomas , E. , Coppo , P. , Marafioti , T. , Emile , J.F. , Larue , M.D. , Schmitt , C. and Gaulard , P. 2010 . Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type . Blood , 115 : 1226 – 1237 .
   PubMed Web of Science ®Google Scholar
• Manley , P.J. , Balitza , A.E. , Bilodeau , M.T. , Coll , K.E. , Hartman , G.D. , McFall , R.C. , Rickert , K.W. , Rodman , L.D. and Thomas , K.A. 2003 . 2,4-Disubstituted pyrimidines: A novel class of KDR kinase inhibitors . Bioorg. Med. Chem. Lett. , 13 : 1673 – 1677 .
   PubMedGoogle Scholar
• Dai , Y. , Hartandi , K. , Soni , N.B. , Pease , L.J. , Reuter , D.R. , Olson , A.M. , Osterling , D.J. , Doktor , S.Z. , Albert , D.H. , Bouska , J.J. , Glaser , K.B. , Marcotte , P.A. , Stewart , K.D. , Davidsen , S.K. and Michaelides , M.R. 2008 . Identification of aminopyrazolopyridine ureas as potent VEGFR/PDGFR multitargeted kinase inhibitors . Bioorg. Med. Chem. Lett. , 18 : 386 – 390 .
   PubMed Web of Science ®Google Scholar
• Kuethe , J.T. , Wong , A. , Qu , C. , Smitrovich , J. , Davies , I.W. and Hughes , D.L. 2004 . Synthesis of 5-substituted-1H-indol-2-yl-1H-quinolin-2-ones: A novel class of KDR kinase inhibitors . J. Org. Chem. , 70 : 2555 – 2567 .
   Google Scholar
• Kiselyov , A.S. , Semenova , M. , Semenovc , V.V. and Piatnitski , E. 2006 . 2-((1H-Azol-1-yl)methyl)-N-arylbenzamides: Novel dual inhibitors of VEGFR-1/2 kinases . Bioorg. Med. Chem. Lett. , 16 : 1726 – 1730 .
   PubMedGoogle Scholar
• Dinges , J. , Zanze , I.A. , Arnold , L.D. , Bousquet , F. , Cunha , G.A. , Ericsson , A.M. , Iwasaki , N. , Michaelides , M.R. , Ogawa , N. , Phelan , K.M. , Rafferty , P. , Sowin , T.J. , Stewart , K.D. , Tokuyama , R. , Xiaa , Z. and Zhang , H.Q. 2006 . Hit-to-lead optimization of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of KDR kinase inhibitors . Bioorg. Med. Chem. Lett. , 16 : 4371 – 4375 .
   PubMedGoogle Scholar
• Baindur , N. , Chadha , N. , Brandt , B.M. , Asgari , D. , Patch , R.J. , Schalk , C. , Carver , T.E. , Petrounia , I.P. , Baumann , C.A. , Ott , H. , Manthey , C. , Springer , B.A. and Player , M.R. 2005 . 2-Hydroxy-4,6-diamino-[1,3,5]triazines: A novel class of VEGF-R2 (KDR) tyrosine kinase inhibitors . J. Med. Chem. , 48 : 1717 – 1720 .
   PubMedGoogle Scholar
• Cristofanilli , M. , Charnsangavej , C. and Hortobagyi , G.N. 2002 . Angiogenesis modulation in cancer research: novel clinical approaches . Nature Rev. , 1 : 415 – 426 .
   Google Scholar
• Pien , H.H. , Fischman , A.J. , Thrall , J.H. and Sorensen , A.G. 2005 . Using imaging biomarkers to accelerate drug development and clinical trials . Drug Discov. Today , 10 : 259 – 266 .
   PubMed Web of Science ®Google Scholar
• Morabito , A. , Piccirillo , M.C. , Falasconi , F. , Feo , G.D. , Giudice , A.D. , Bryce , J. , Maio , M.D. , Maio , E.D. , Normanno , N. and Perrone , F. 2009 . Vandetanib (ZD6474), a dual inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) tyrosine kinases: Current status and future directions . The Oncologist , 14 : 378 – 390 .
   PubMed Web of Science ®Google Scholar
• Gauler , T.C. , Besse , B. , Mauguen , A. , Meric , J.B. , Gounant , V. , Fischer , B. , Overbeck , T.R. , Krissel , H. , Laurent , D. , Tiainen , M. , Commo , F. , Soria , J.C. and Eberhardt , W.E.E. 2012 . Phase II trial of PTK787/ZK 222584 (Vatalanib) administered orally once-daily or in two divided daily doses as second-line monotherapy in relapsed or progressing patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) . Ann. Oncol. , 23 : 678 – 687 .
   PubMed Web of Science ®Google Scholar
• M.I. El-Gamal, H.S. Anbar, K.H. Yoo, and C.H. Oh, FMS kinase inhibitors: Current status and future prospects, Med. Res. Rev. (2012), DOI 10.1002.
   Google Scholar
• Asahina , H. , Tamura , Y. , Nokihara , H. , Yamamoto , N. , Seki , Y. , Shibata , T. , Goto , Y. , Tanioka , M. , Yamada , Y. , Coates , A. , Chiu , Y.L. , Li , Xiaohui , Pradhan , R. , Ansell , P. J. , McKeegan , E. M. , McKee , M. D. , Carlson , D. M. and Tamura , T. 2012 . An open-label, phase 1 study evaluating safety, tolerability, and pharmacokinetics of linifanib (ABT-869) in Japanese patients with solid tumors . Cancer Chemother. Pharmacol. , 69 : 1477 – 1486 .
   PubMed Web of Science ®Google Scholar
• Gracias , V. , Ji , Z. , Zanze , I.A. , Zapatero , C.A. , Huth , J.R. , Song , D. , Hajduk , P.J. , Johnson , E.F. , Glaser , K.B. , Marcotte , P.A. , Pease , L. , Soni , N.B. , Stewart , K.D. , Davidsen , S.K. , Michaelides , M.R. and Djuric , S.W. 2008 . Scaffold oriented synthesis. Part 2: Design, synthesis and biological evaluation of pyrimido-diazepines as receptor tyrosine kinase inhibitors . Bioorg. Med. Chem. Lett. , 18 : 2691 – 2695 .
   PubMed Web of Science ®Google Scholar
• Ji , Z. , Ahmed , A.A. , Albert , D.H. , Bouska , J.J. , Bousquet , P.F. , Cunha , G.A. , Diaz , G. , Glaser , K.B. , Guo , J. , Harris , C.M. , Li , J. , Marcotte , P.A. , Moskey , M.D. , Oie , T. , Pease , L. , Soni , N.B. , Stewart , K.D. , Davidsen , S.K. and Michaelides , M.R. 2008 . 3-Amino-benzo[d]isoxazoles as novel multitargeted inhibitors of receptor tyrosine kinases . J. Med. Chem. , 51 : 1231 – 1241 .
   PubMedGoogle Scholar
• Zanzel , A. , Albert , D.H. , Bousquet , P.F. , Cunha , G.A. , Harris , C.M. , Moskey , M. , Dinges , J. , Stewart , K.D. and Sowin , T.J. 2007 . Synthesis and biological evaluation of 5-substituted 1,4-dihydroindeno[1,2-c]pyrazoles as multitargeted receptor tyrosine kinase inhibitors . Bioorg. Med. Chem. Lett. , 17 : 3136 – 3140 .
   PubMedGoogle Scholar
• Cronin , M.T.D. and Schultz , T.W. 2003 . Pitfalls in QSAR . J. Mol. Struc. , 622 : 39 – 51 .
   Web of Science ®Google Scholar
• Phase, version 3.3, Schrödinger, LLC, New York, 2011.
   Google Scholar
• Dixon , S.L. , Smondyrev , A.M. , Knoll , E.H. , Rao , S.N. , Shaw , D.E. and Friesner , R.A. 2006 . PHASE: a new engine for pharmacophore perception, 3D QSAR model development, and 3D database screening: 1. Methodology and preliminary results . J. Comput. Aided Mol. Des. , 20 : 647 – 671 .
   PubMed Web of Science ®Google Scholar
• Jorgensen , W.L. and Tirado , R.J. 1988 . The OPLS force field for proteins. Energy minimizations for crystals of cyclic peptides and crambin . J. Am. Chem. Soc. , 110 : 1657 – 1666 .
   PubMed Web of Science ®Google Scholar
• Watts , K.S. , Dalal , P. , Murphy , R.B. , Sherman , W. , Friesner , R.A. and Shelley , J.C. 2010 . Confromational search method for efficient generation of bioactive conformers . J. Chem. Inf. Model. , 50 : 534 – 546 .
   PubMed Web of Science ®Google Scholar
• Tropsha , A. , Gramatica , P. and Gombar , V.K. 2003 . The importance of being earnest: Validation is the absolute essential for successful application and interpretation of QSPR models . QSAR Comb. Sci. , 22 : 69 – 77 .
   Google Scholar
• Gramatica , P. 2007 . Principles of QSAR models validation: internal and external . QSAR Comb. Sci. , 26 : 694 – 701 .
   Google Scholar
• Hawkins , D.M. , Basak , S.C. and Mills , D. 2003 . Assessing model fit by cross-validation . J. Chem. Inf. Comput. Sci. , 43 : 579 – 586 .
   PubMedGoogle Scholar
• Guha , R. and Jurs , P.C. 2005 . Determining the validity of a QSAR model - A classification approach . J. Chem. Inf. Model. , 45 : 65 – 73 .
   PubMed Web of Science ®Google Scholar
• Golbraikh , A. and Tropsha , A. 2002 . Beware of q2! . J. Mol. Graph. Model. , 20 : 269 – 276 .
   PubMed Web of Science ®Google Scholar
• Consonni , V. , Ballabio , D. and Todeschini , R. 2009 . Comments on the definition of the Q2 parameter for QSAR validation . J. Chem. Inf. Model. , 49 : 1669 – 1678 .
   PubMed Web of Science ®Google Scholar
• Kubinyi , H. 1997 . QSAR and 3D QSAR in drug design Part 1: Methodology . Drug Discov. Today , 2 : 457 – 467 .
   Web of Science ®Google Scholar
• Kubinyi , H. 1997 . QSAR and 3D QSAR in drug design Part 2: Applications and problems . Drug Discov. Today , 2 : 538 – 546 .
   Web of Science ®Google Scholar
• Golbraikh , A. and Tropsha , A. 2002 . Predictive QSAR modeling based on diversity sampling of experimental datasets for the training and test set selection . J. Comput. Aided Mol. Des. , 16 : 357 – 369 .
   PubMed Web of Science ®Google Scholar
• Doweyko , A.M. 2004 . 3D-QSAR illusions . J. Comput. Aided Mol. Des. , 18 : 587 – 596 .
   PubMed Web of Science ®Google Scholar
• Schuurmann , G. , Ebert , R.U. , Chen , J. , Wang , B. and Kuhne , R. 2008 . External validation and prediction employing the predictive squared correlation coefficients test set activity mean vs. training set activity mean . J. Chem. Inf. Model. , 48 : 2140 – 2145 .
   PubMed Web of Science ®Google Scholar
• Mitra , I. , Roy , P.P. , Kar , S. , Ojha , P.K. and Roy , K. 2009 . On further application of rm 2 as a metric for validation of QSAR models . J. Chemom. , 24 : 22 – 33 .
   Google Scholar
• Glide, version 5.7, Schrödinger, LLC, New York, 2011.
   Google Scholar
• Friesner , R.A. , Banks , J.L. , Murphy , R.B. , Halgren , T.A. , Klicic , J.J. , Mainz , D.T. , Repasky , M.P. , Knoll , E.H. , Shelley , M. , Perry , J.K. , Shaw , D.E. , Francis , P. and Shenkin , P.S. 2004 . Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy . J. Med. Chem. , 47 : 1739 – 1749 .
   PubMed Web of Science ®Google Scholar
• Miyazaki , Y. , Matsunaga , S. , Tang , J. , Maeda , Y. , Nakano , M. , Philippe , R.J. , Shibahara , M. , Liu , W. , Sato , H. , Wangb , L. and Nolteb , R.T. 2005 . Novel 4-amino-furo[2,3-d]pyrimidines as Tie-2 and VEGFR2 dual inhibitors . Bioorg. Med. Chem. Lett. , 15 : 2203 – 2207 .
   PubMed Web of Science ®Google Scholar
• Desmond Molecular Dynamics System, version 3.0, D.E. Shaw Research, New York, 2011.
   Google Scholar
• Maestro-Desmond Interoperability Tools, version 3.0, Schrodinger, New York, 2011.
   Google Scholar
• Mackerell , A.D. , Bashford , D. , Bellott , M. , Dunbrack , R.L. , Evanseck , J.D. , Field , M.J. , Fischer , S. , Gao , J. , Guo , H. , Ha , S. , McCarthy , D.J. , Kuchnir , L. , Kuczera , K. , Lau , F.T.K. , Mattos , C. , Michnick , S. , Ngo , T. , Nguyen , D.T. , Prodhom , B. , Reiher , W.E. , Roux , B. , Schlenkrich , M. , Smith , J.C. , Stote , R. , Straub , J. , Watanabe , M. , Kuczera , W. , Yin , D. and Karplus , M. 1998 . All-atom empirical potential for molecular modeling and dynamics studies of proteins . J. Phys. Chem. B , 102 : 3586 – 3616 .
   PubMed Web of Science ®Google Scholar
• Ryckaert , J.P. , Ciccotti , G. and Berendsen , H.J.C. 1997 . Numerical integration of the Cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes . J. Comput. Phys. , 23 : 327 – 341 .
   Web of Science ®Google Scholar
• Zeng , H. and Zhang , H. 2010 . Combined 3D-QSAR modeling and molecular docking study on 1,4-dihydroindeno[1,2-c]pyrazoles as VEGFR-2 kinase inhibitors . J. Mol. Graph. Model. , 29 : 54 – 71 .
   PubMedGoogle Scholar
• Du , J. , Lei , B. , Qin , J. , Liu , H. and Yao , X. 2009 . Molecular modeling studies of vascular endothelial growth factor receptor tyrosine kinase inhibitors using QSAR and docking . J. Mol. Graph. Model. , 27 : 642 – 654 .
   PubMedGoogle Scholar
• Pasha , F.A. , Muddassar , M. , Neaz , M.M. and Cho , S.J. 2009 . Pharmacophore and docking-based combined in-silico study of KDR inhibitors . J. Mol. Graph. Model. , 28 : 54 – 61 .
   PubMedGoogle Scholar
• Abreu , R.M.V. , Froufe , H.J.C. , Queiroz , M.R.P. and Ferreira , I.C.F.R. 2012 . Selective flexibility of side-chain residues improves VEGFR-2 docking score using AutoDock Vina . Chem. Biol. Drug Des. , 79 : 530 – 534 .
   PubMed Web of Science ®Google Scholar