Inhibition of Tumor Cell Growth, Invasion, and Metastasis by EXEL-2880 (XL880, GSK1363089), a Novel Inhibitor of HGF and VEGF Receptor Tyrosine Kinases
Published version of a preprint
Abstract
The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are overexpressed and/or activated in a wide variety of human malignancies. Vascular endothelial growth factor (VEGF) receptors are expressed on the surface of vascular endothelial cells and cooperate with Met to induce tumor invasion and vascularization. EXEL-2880 (XL880, GSK1363089) is a small-molecule kinase inhibitor that targets members of the HGF and VEGF receptor tyrosine kinase families, with additional inhibitory activity toward KIT, Flt-3, platelet-derived growth factor receptor β, and Tie-2. Binding of EXEL-2880 to Met and VEGF receptor 2 (KDR) is characterized by a very slow off-rate, consistent with X-ray crystallographic data showing that the inhibitor is deeply bound in the Met kinase active site cleft. EXEL-2880 inhibits cellular HGF-induced Met phosphorylation and VEGF-induced extracellular signal-regulated kinase phosphorylation and prevents both HGF-induced responses of tumor cells and HGF/VEGF-induced responses of endothelial cells. In addition, EXEL-2880 prevents anchorage-independent proliferation of tumor cells under both normoxic and hypoxic conditions. In vivo, these effects produce significant dose-dependent inhibition of tumor burden in an experimental model of lung metastasis. Collectively, these data indicate that EXEL-2880 may prevent tumor growth through a direct effect on tumor cell proliferation and by inhibition of invasion and angiogenesis mediated by HGF and VEGF receptors. [Cancer Res 2009;69(20):8009–16]
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Crystal structures of foretinib in complex with c-Met, EphA2, and STK10 have been solved.
“Crystal structures of foretinib in complex with three different kinases have been solved to date (c-Met, EphA2, and STK10) 64, 65”
From Rationalizing PROTAC-Mediated Ternary Complex Formation Using Rosetta (2021) · cites this paper as [64]
Cites
The biology of VEGF and its receptors
Ferrara, N., Gerber, H.-P., & LeCouter, J. (2003) · Nature Medicine · doi:10.1038/nm0603-669 · Cited by 9,591 · see citing works
<i>MET</i> Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
Engelman, J. A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J. O., Lindeman, N., Gale, C.-M., Zhao, X., Christensen, J., et al. (2007) · Science · doi:10.1126/science.1141478 · Cited by 4,496 · see citing works
Met, metastasis, motility and more
Birchmeier, C., Birchmeier, W., Gherardi, E., & Woude, G. V. (2003) · Nature reviews. Molecular cell biology · doi:10.1038/nrm1261 · Cited by 2,667 · see citing works
Bean, J., Brennan, C., Shih, J.-Y., Riely, G., Viale, A., Wang, L., Chitale, D., Motoi, N., Szoke, J., Broderick, S., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710370104 · Cited by 1,598 · see citing works
Schmidt, L. S., Duh, F.-M. C., Chen, F., Kishida, T., Glenn, G. M., Choyke, P. L., Scherer, S. W., Zhuang, Z., Lubensky, I. A., Dean, M. C., et al. (1997) · Nature Genetics · doi:10.1038/ng0597-68 · Cited by 1,517 · see citing works
Active and Inactive Protein Kinases: Structural Basis for Regulation
Johnson, L. N., Noble, M. E. M., & Owen, D. J. (1996) · Cell · doi:10.1016/s0092-8674(00)81092-2 · Cited by 1,396 · see citing works
Bergers, G., Song, S., Meyer-Morse, N., Bergsland, E. K., & Hanahan, D. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17929 · Cited by 1,361 · see citing works
Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene
Pennacchietti, S., Michieli, P., Galluzzo, M., Mazzone, M., Giordano, S., & Comoglio, P. M. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00085-0 · Cited by 1,311 · see citing works
Bergers, G., Song, S., Meyer-Morse, N., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317929 · Cited by 1,192 · see citing works
Drug development of MET inhibitors: targeting oncogene addiction and expedience
Comoglio, P. M., Giordano, S., & Trusolino, L. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2530 · Cited by 822 · see citing works
Huh, C.-G., Factor, V. M., Sánchez, A., Uchida, K., Conner, E. A., & Thorgeirsson, S. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306068101 · Cited by 750 · see citing works
Biological behavior of malignant melanoma cells correlated to their survival in vivo.
Fidler, I. J. (1975) · PubMed · Cited by 592 · see citing works
Nakajima, M., SAWADA, H., Yamada, Y., Watanabe, A., Tatsumi, M., Yamashita, J., Matsuda, M., SAKAGUCHI, T., Hirao, T., & Nakano, H. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19990501)85:9%3c1894::aid-cncr3%3e3.0.co;2-j · Cited by 494 · see citing works
Ma, P. C., Kijima, T., Maulik, G., Fox, E. A., Sattler, M., Griffin, J. D., Johnson, B. E., & Salgia, R. (2003) · PubMed · Cited by 454 · see citing works
Takayama, H., LaRochelle, W. J., Sharp, R., Otsuka, T., Kriebel, P., Anver, M. R., Aaronson, S. A., & Merlino, G. T. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.2.701 · Cited by 442 · see citing works
Xin, X., Yang, S., Ingle, G. S., Zlot, C. H., Rangell, L. K., Kowalski, J., SCHWALL, R. H., Ferrara, N., & Gerritsen, M. E. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64058-8 · Cited by 397 · see citing works
Rong, S., Segal, S., Anver, M. R., Resau, J. H., & Woude, G. F. V. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.11.4731 · Cited by 365 · see citing works
Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas
Renzo, M. F. D., Olivero, M., Martone, T., Maffé, A., Maggiora, P., Stefani, A. D., Valente, G., Giordano, S., Cortesina, G., & Comoglio, P. M. (2000) · Oncogene · doi:10.1038/sj.onc.1203455 · Cited by 334 · see citing works
A novel germ line juxtamembrane Met mutation in human gastric cancer
Lee, J., Han, S.-U., Cho, H., Jennings, B. A., Gerrard, B., Dean, M. C., Schmidt, L. S., Zbar, B., & Woude, G. F. V. (2000) · Oncogene · doi:10.1038/sj.onc.1203874 · Cited by 330 · see citing works
Frequent amplification of the c-met gene in scirrhous type stomach cancer
Kuniyasu, H., Yasui, W., Kitadai, Y., Yokozaki, H., Ito, H., & 田原, 榮. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)91548-5 · Cited by 329 · see citing works
A Novel One-Armed Anti-c-Met Antibody Inhibits Glioblastoma Growth In vivo
Martens, T., Schmidt, N. O., Eckerich, C., Fillbrandt, R., Merchant, M. A., SCHWALL, R. H., Westphal, M., & Lamszus, K. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1418 · Cited by 305 · see citing works
Lengyel, E. R., Prechtel, D., Resau, J. H., Gauger, K., Welk, A., Lindemann, K. Y., Salanti, G., Richter, T., Knudsen, B. S., Woude, G. F. V., et al. (2004) · International Journal of Cancer · doi:10.1002/ijc.20598 · Cited by 273 · see citing works
Burgess, T. L., Coxon, A., MEYER, S. R., Sun, J., Rex, K. L., Tsuruda, T. S., Chen, Q., Ho, S.-Y., Li, L. Z., Kaufman, S., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3329 · Cited by 252 · see citing works
Park, W. S., Dong, S. M., Kim, S. Y., Na, E. Y., Shin, M. S., Pi, J. H., Kim, B. J., Bae, J. H., Hong, Y. K., Lee, K. S., et al. (1999) · PubMed · Cited by 251 · see citing works
The MET oncogene drives a genetic programme linking cancer to haemostasis
Boccaccio, C., Sabatino, G., Médico, E., Girolami, F., Follenzi, A., Reato, G., Sottile, A., Naldini, L., & Comoglio, P. M. (2005) · Nature · doi:10.1038/nature03357 · Cited by 250 · see citing works
Cao, B. B., Su, Y., Oskarsson, M. K., Zhao, P., Kort, E. J., Fisher, R. J., Wang, L.-M., & Woude, G. F. V. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.131200498 · Cited by 213 · see citing works
Abounader, R., Lal, B., Luddy, C., Koe, G. S., Davidson, B. L., Rosen, E. M., & Laterra, J. (2001) · The FASEB Journal · doi:10.1096/fj.01-0421fje · Cited by 186 · see citing works
c-Met gene amplification is associated with advanced stage colorectal cancer and liver metastases
Zeng, Z., Weiser, M. R., Kuntz, E. J., Chen, C., Khan, S. A., Forslund, A., Nash, G. M., Gimbel, M. I., Yamaguchi, Y., Culliford, A. T., et al. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.02.049 · Cited by 181 · see citing works
Bellusci, S., Moens, G., Gaudino, G., Comoglio, P. M., Nakamura, T., Thiery, J. P., & Jouanneau, J. (1994) · PubMed · Cited by 168 · see citing works
Out of air is not out of action
Bottaro, D. P., & Liotta, L. A. (2003) · Nature · doi:10.1038/423593a · Cited by 168 · see citing works
Schiering, N., Knapp, S., Marconi, M., Flocco, M. M., Cui, J., Perego, R., Rusconi, L., & Cristiani, C. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1734128100 · Cited by 156 · see citing works
Tomioka, D., Maehara, N., Kuba, K., Mizumoto, K., Tanaka, M., Matsumoto, K., & Nakamura, T. (2001) · PubMed · Cited by 151 · see citing works
Bellon, S. F., Kaplan‐Lefko, P. J., Yang, Y., Zhang, Y., Moriguchi, J., Rex, K. L., Johnson, C. W., Rose, P., Long, A. M., O'Connor, A. B., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705774200 · Cited by 140 · see citing works
Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents
Laird, A., & Cherrington, J. M. (2003) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.12.1.51 · Cited by 129 · see citing works
Lorenzato, A., Olivero, M., Patanè, S., Rosso, E., OLIARO, A., Comoglio, P. M., & Renzo, M. F. D. (2002) · PubMed · Cited by 124 · see citing works
Differential gene expression in colon carcinoma cells and tissues detected with a cDNA array
Backert, S., Gelos, M., Kobalz, U., Hanski, M., B�hm, C., Mann, B., L�vin, N., Gratchev, A. N., Mannsmann, U., Moyer, M. P., et al. (1999) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19990909)82:6 · Cited by 105 · see citing works
Wang, W., Marimuthu, A., Tsai, J. Y., Kumar, A., Krupka, H. I., Zhang, C., Powell, B., Suzuki, Y., Nguyen, H. T., Tabrizizad, M., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600048103 · Cited by 84 · see citing works
Kim, S. J., Johnson, M., Koterba, K. L., Herynk, M. H., Uehara, H., & Gallick, G. E. (2003) · PubMed · Cited by 83 · see citing works
Baykal, C. M., Ayhan, A., Al, R. A., Yuce, K., & Ayhan, A. (2003) · Gynecologic Oncology · doi:10.1016/s0090-8258(02)00073-2 · Cited by 77 · see citing works
Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors
Cai, Z., Wei, D. D., Schroeder, G. M., Cornelius, L. A. M., Kim, K., Chen, X., Schmidt, R. J., Williams, D. K., Tokarski, J. S., An, Y., et al. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.04.047 · Cited by 66 · see citing works
Clinical Significance of c-met Oncogene Alterations in Human Colorectal Cancer
Umeki, K., Shiota, G., & Kawasaki, H. (1999) · Oncology · doi:10.1159/000011985 · Cited by 64 · see citing works
Lin, H.-L., Liu, T., Lui, W., & Chi, C. (1999) · Cancer · doi:10.1002/(sici)1097-0142(19990501)85:9 · Cited by 57 · see citing works
Seruca, R., Suijkerbuijk, R. F., Gärtner, F., Criado, M. B., Veiga, I., Olde-Weghuis, D., David, L., Castedo, S. M. M. J., & Sobrinho-Simões, M. A. (1995) · Cancer Genetics and Cytogenetics · doi:10.1016/0165-4608(95)00033-l · Cited by 48 · see citing works
Inhibition of human non-small cell lung tumors by a c-Met antisense/U6 expression plasmid strategy
Stabile, L. P., Lyker, J. S., Huang, L., & Siegfried, J. (2004) · Gene Therapy · doi:10.1038/sj.gt.3302169 · Cited by 47 · see citing works
Wu, F., WU, L., Zheng, S., Ding, W., Teng, L., Wang, Z., Ma, Z., & ZHAO, W. (2006) · Digestive and Liver Disease · doi:10.1016/j.dld.2006.03.007 · Cited by 42 · see citing works
Kawano, R., Ohshima, K., Karube, K., Yamaguchi, T., Kohno, S., Suzumiya, J., Kikuchi, M., & Tamura, K. (2004) · British Journal of Haematology · doi:10.1111/j.1365-2141.2004.05197.x · Cited by 29 · see citing works
Sepp‐Lorenzino, L., Rands, E., Mao, X., Connolly, B., Shipman, J. M., Antanavage, J., Hill, S., Davis, L. J., Beck, S. C., Rickert, K. W., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2871 · Cited by 27 · see citing works
Evaluation of the tyrosine kinase domain of theMet Proto-oncogene in sporadic ovarian carcinomas
Tanyi, J. L., Tory, K., Rigó, J. J., Nagy, B., & Papp, Z. (1999) · Pathology & Oncology Research · doi:10.1053/paor.1999.0219 · Cited by 25 · see citing works
Missense Mutation of the MET Gene Detected in Human Glioma
Moon, Y.-W., Weil, R. J., Pack, S., Park, W.-S., Pak, E. D., Pham, T., Karkera, J. D., Kim, H.-K., Vortmeyer, A. O., Fuller, B. G., et al. (2000) · Modern Pathology · doi:10.1038/modpathol.3880177 · Cited by 22 · see citing works
SPORADIC BILATERAL PAPILLARY RENAL CARCINOMA EXHIBITING C-MET MUTATION IN THE LEFT KIDNEY TUMOR
Takaki, Y., Furihata, M., YOSHIKAWA, C., Kishida, T., Yao, M., & Shuin, T. (2000) · The Journal of Urology · doi:10.1016/s0022-5347(05)67735-x · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Targeting MET in cancer: rationale and progress
Gherardi, E., Birchmeier, W., Birchmeier, C., & Woude, G. V. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3205 · Cited by 1,420 · see citing works
Yakes, F. M., Chen, J., Tan, J., Yamaguchi, T., Shi, Y., Yu, P., Qian, F., Chu, F., Bentzien, F., Cancilla, B., et al. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0264 · Cited by 1,350 · see citing works
Self-citationActivation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer
Zhang, Z., Lee, J. C., Lin, L., Olivas, V., Au, V., LaFramboise, T., Abdel-Rahman, M., Wang, X., Levine, A. D., Rho, J. K., et al. (2012) · Nature Genetics · doi:10.1038/ng.2330 · Cited by 1,224 · see citing works
Talele, T. T. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00472 · Cited by 1,049 · see citing works
Lessons in PROTAC Design from Selective Degradation with a Promiscuous Warhead
Bondeson, D. P., Smith, B. E., Burslem, G. M., Buhimschi, A. D., Hines, J., Jaime-Figueroa, S., Wang, J., Hamman, B. D., Ishchenko, A., & Crews, C. M. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.09.010 · Cited by 923 · see citing works
Cooke, V. G., LeBleu, V. S., Keskin, D., Khan, Z., O'Connell, J. T., Teng, Y., Duncan, M. B., Xie, L., Maeda, G., Vong, S., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2011.11.024 · Cited by 530 · see citing works
MET is required for the recruitment of anti-tumoural neutrophils
Finisguerra, V., Conza, G. D., Matteo, M. D., Serneels, J., Costa, S., Thompson, A. A. R., Wauters, E., Walmsley, S. R., Prenen, H., Granot, Z., et al. (2015) · Nature · doi:10.1038/nature14407 · Cited by 494 · see citing works
Zhu, C., Wei, Y., & Wei, X. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1090-3 · Cited by 498 · see citing works
Choueiri, T. K., Vaishampayan, U. N., Rosenberg, J. E., Logan, T. F., Harzstark, A. L., Bukowski, R. M., Rini, B. I., Srinivas, S., Stein, M. N., Adams, L. M., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.43.3383 · Cited by 462 · see citing works
Sennino, B., Ishiguro‐Oonuma, T., Wei, Y., Naylor, R. M., Williamson, C. W., Bhagwandin, V. J., Tabruyn, S. P., You, W., Chapman, H. A., Christensen, J. G., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0240 · Cited by 404 · see citing works
c-MET as a potential therapeutic target and biomarker in cancer
Sierra, J. R., & Tsao, M. (2011) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758834011422557 · Cited by 367 · see citing works
Phenotypic drug discovery: recent successes, lessons learned and new directions
Vincent, F., Nueda, A., Lee, J. L. C., Schenone, M., Prunotto, M., & Mercola, M. A. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00472-w · Cited by 372 · see citing works
Okamura, R., Boichard, A., Kato, S., Sicklick, J. K., Bazhenova, L., & Kurzrock, R. (2018) · JCO Precision Oncology · doi:10.1200/po.18.00183 · Cited by 328 · see citing works
Targeting the HGF/c-MET Pathway in Hepatocellular Carcinoma
Goyal, L., Muzumdar, M. D., & Zhu, A. X. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2791 · Cited by 307 · see citing works
KLIFS: A Knowledge-Based Structural Database To Navigate Kinase–Ligand Interaction Space
van Linden, O. P. J., Kooistra, A. J., Leurs, R., de Esch, I. J. P., & de Graaf, C. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400378w · Cited by 303 · see citing works
MET: a promising anticancer therapeutic target
Peters, S., & Adjei, A. A. (2012) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2012.71 · Cited by 280 · see citing works
VEGF and c-Met Blockade Amplify Angiogenesis Inhibition in Pancreatic Islet Cancer
You, W., Sennino, B., Williamson, C. W., Falcón, B. L., Hashizume, H., Yao, L., Aftab, D. T., & McDonald, D. M. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2527 · Cited by 262 · see citing works
Cytokine networking of innate immunity cells: a potential target of therapy
Střı́ž, I., Brabcová, E., Kolesár, L., & Sekerková, A. (2014) · Clinical Science · doi:10.1042/cs20130497 · Cited by 224 · see citing works
Targeting Receptor Tyrosine Kinase MET in Cancer: Small Molecule Inhibitors and Clinical Progress
Cui, J. J. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm401427c · Cited by 216 · see citing works
Shah, M. A., Wainberg, Z. A., Catenacci, D. V. T., Höchster, H. S., Ford, J. M., Kunz, P. L., Lee, F.-C., Kallender, H., Cecchi, F., Rabe, D. C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054014 · Cited by 210 · see citing works
AXL Inhibitors in Cancer: A Medicinal Chemistry Perspective
Myers, S. H., Brunton, V. G., & Unciti‐Broceta, A. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01273 · Cited by 210 · see citing works
MSP–RON signalling in cancer: pathogenesis and therapeutic potential
Yao, H., Zhou, Y.-Q., Zhang, R., & Wang, M. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3545 · Cited by 206 · see citing works
Eder, J. P., Shapiro, G. I., Appleman, L. J., Zhu, A. X., Miles, D., Keer, H. N., Cancilla, B., Chu, F., Hitchcock‐Bryan, S., Sherman, L. J., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0574 · Cited by 198 · see citing works
The clinical and functional significance of c-Met in breast cancer: a review
Ho-Yen, C., Jones, J. L., & Kermorgant, S. (2015) · Breast Cancer Research · doi:10.1186/s13058-015-0547-6 · Cited by 197 · see citing works
Anoikis and EMT: Lethal "Liaisons" during Cancer Progression
Cao, Z., Livas, T., & Kyprianou, N. (2016) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.2016016955 · Cited by 191 · see citing works
Vascular Endothelial Growth Factor (VEGF) Receptors: Drugs and New Inhibitors
Musumeci, F., Radi, M., Brullo, C., & Schenone, S. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm301085w · Cited by 187 · see citing works
Systemic treatment of renal cell cancer: A comprehensive review
Sánchez-Gastaldo, A., Kempf, E., del Alba, A. G., & Durán, I. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2017.08.010 · Cited by 174 · see citing works
Receptor Tyrosine Kinase Coactivation Networks in Cancer
Xu, A. M., & Huang, P. H. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0163 · Cited by 174 · see citing works
Rationalizing PROTAC-Mediated Ternary Complex Formation Using Rosetta
Bai, N., Miller, S. A., Andrianov, G. V., Yates, M., Kirubakaran, P., & Karanicolas, J. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c01451 · Cited by 157 · see citing works
Recent advances in the discovery of small molecule c-Met Kinase inhibitors
Parikh, P. K., & Ghate, M. D. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.08.044 · Cited by 157 · see citing works
Soltan, O. M., Shoman, M. E., Abdel‐Aziz, S. A., Narumi, A., Konno, H., & Abdel‐Aziz, M. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113768 · Cited by 148 · see citing works
Jia, H., Dai, G., Weng, J., Zhang, Z., Wang, Q., Zhou, F., Jiao, L., Cui, Y., Ren, Y., Fan, S., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500510f · Cited by 144 · see citing works
Papillary renal cell carcinoma: A review of the current therapeutic landscape
Courthod, G., Tucci, M., Maïo, M. D., & Scagliotti, G. V. (2015) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2015.05.008 · Cited by 141 · see citing works
Small Molecule Kinase Inhibitors for the Treatment of Brain Cancer
Heffron, T. P. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00618 · Cited by 141 · see citing works
Tiedt, R., Degenkolbe, E., Furet, P., Appleton, B. A., Wagner, S., Schoepfer, J. G., Buck, E., Ruddy, D. A., Monahan, J. E., Jones, M. D., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-4433 · Cited by 136 · see citing works
Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy
Riquelme, I., Saavedra, K., Espinoza, J. A., Weber, H. L., García, P., Nervi, B., Marcelo Garrido, S., Corvalán, A. H., Roa, J. C., & Bizama, C. (2015) · Oncotarget · doi:10.18632/oncotarget.4990 · Cited by 133 · see citing works
Recent development of multi-target VEGFR-2 inhibitors for the cancer therapy
Liu, X., Zhao, H.-C., Hou, S.-J., Zhang, H., Cheng, L., Yuan, S., Zhang, L., Song, J., Zhang, S., & Chen, S. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.106425 · Cited by 133 · see citing works
Kinase Inhibitors of Marine Origin
Bharate, S. B., Sawant, S. D., Singh, P. P., & Vishwakarma, R. A. (2013) · Chemical Reviews · doi:10.1021/cr300410v · Cited by 130 · see citing works
Molecularly targeted therapy in hepatocellular carcinoma
Huynh, H. T. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.03.034 · Cited by 127 · see citing works
Kataoka, Y., Mukohara, T., Tomioka, H., Funakoshi, Y., Kiyota, N., Fujiwara, Y., Yashiro, M., Hirakawa, K., Hirai, M., & Minami, H. (2011) · Investigational New Drugs · doi:10.1007/s10637-011-9699-0 · Cited by 118 · see citing works
Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins
Davare, M. A., Saborowski, A. L., Eide, C. A., Tognon, C. E., Smith, R. L., Elferich, J., Agarwal, A., Tyner, J. W., Shinde, U. P., Lowe, S. W., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1319583110 · Cited by 117 · see citing works
Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors
Davare, M. A., Vellore, N. A., Wagner, J. P., Eide, C. A., Goodman, J. R., Drilon, A. E. D. C., Deininger, M. W., O’Hare, T., & Druker, B. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515281112 · Cited by 116 · see citing works
Patwardhan, P. P., Ivy, K. S., Musi, E., de Stanchina, E., & Schwartz, G. K. (2015) · Oncotarget · doi:10.18632/oncotarget.6547 · Cited by 116 · see citing works
Zillhardt, M., Park, S.-M., Romero, I. L., Sawada, K., MONTAG, A. G., Krausz, T. N., Yamada, S. D., Peter, M. E., & Lengyel, E. R. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3387 · Cited by 116 · see citing works
Smyth, E. C., Sclafani, F., & Cunningham, D. (2014) · OncoTargets and Therapy · doi:10.2147/ott.s44941 · Cited by 114 · see citing works
Immunologically augmented cancer treatment using modern radiotherapy
Durante, M., Reppingen, N., & Held, K. D. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.05.007 · Cited by 111 · see citing works
Mechanisms of Resistance to NTRK Inhibitors and Therapeutic Strategies in NTRK1-Rearranged Cancers
Fuse, M. J., Okada, K., Oh‐hara, T., Ogura, H., Fujita, N., & Katayama, R. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-16-0909 · Cited by 112 · see citing works
Park, I., Mishra, A., Chandler, J. C., Whitman, S. P., Marcucci, G., & Caligiuri, M. A. (2013) · Blood · doi:10.1182/blood-2012-07-444018 · Cited by 108 · see citing works
Cui, J. J., McTigue, M. A., Nambu, M. D., Tran‐Dubé, M., Pairish, M., Shen, H., Jia, L., Cheng, H., Hoffman, J. E., Le, P., et al. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm300967g · Cited by 108 · see citing works
HGF/c-MET Signaling in Melanocytes and Melanoma
Czyż, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123844 · Cited by 99 · see citing works
Zhang, J. C., Jiang, X., Jiang, Y., Guo, M., Zhang, S., Li, J., He, J., Liu, J., Wang, J., & Ouyang, L. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.12.016 · Cited by 98 · see citing works
MET Signaling: Novel Targeted Inhibition and Its Clinical Development in Lung Cancer
Feng, Y., Thiagarajan, P. S., & Ma, P. C. (2012) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3182417e44 · Cited by 93 · see citing works
Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine
Holbrook, J. D., Parker, J. S., Gallagher, K. T., Halsey, W. S., Hughes, A. M., Weigman, V., Lebowitz, P. F., & Kumar, R. (2011) · Journal of Translational Medicine · doi:10.1186/1479-5876-9-119 · Cited by 93 · see citing works
Seiwert, T. Y., Sarantopoulos, J., Kallender, H., McCallum, S. W., Keer, H. N., & Blumenschein, G. R. (2012) · Investigational New Drugs · doi:10.1007/s10637-012-9861-3 · Cited by 92 · see citing works
Turning liabilities into opportunities: Off-target based drug repurposing in cancer
Palve, V. C., Liao, Y., Rix, L. L. R., & Rix, U. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.02.003 · Cited by 92 · see citing works
Progress in cancer therapy targeting c-Met signaling pathway
Jung, K. H., Park, B. H., & Hong, S. (2012) · Archives of Pharmacal Research · doi:10.1007/s12272-012-0402-6 · Cited by 92 · see citing works
Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches
Choi, H. J., Armaiz-Peña, G. N., Pradeep, S., Cho, M. S., Coleman, R. L., & Sood, A. K. (2014) · Cancer and Metastasis Reviews · doi:10.1007/s10555-014-9538-9 · Cited by 91 · see citing works
Martorana, A., Monica, G. L., & Lauria, A. (2020) · Molecules · doi:10.3390/molecules25184279 · Cited by 90 · see citing works
Chimeric Antigen Receptor (CAR) T Cell Therapy for Metastatic Melanoma: Challenges and Road Ahead
Soltantoyeh, T., Akbari, B., Karimi, A., Chalbatani, G. M., Ghahri-Saremi, N., Hadjati, J., Hamblin, M. R., & Mirzaei, H. R. (2021) · Cells · doi:10.3390/cells10061450 · Cited by 88 · see citing works
Axl Kinase as a Key Target for Oncology: Focus on Small Molecule Inhibitors
Feneyrolles, C., Spenlinhauer, A., Guiet, L., Fauvel, B., Daydé-Cazals, B., Warnault, P., Chevé, G., & Yasri, A. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-1083 · Cited by 83 · see citing works
Furlan, A., Colombo, F., Kövér, A., Issaly, N., Tintori, C., Angeli, L., Leroux, V., Letard, S., Amat, M., Asses, Y., et al. (2011) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2011.10.051 · Cited by 82 · see citing works
Varkaris, A. S., Corn, P. G., Gaur, S., Dayyani, F., Logothetis, C. J., & Gallick, G. E. (2011) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2011.631523 · Cited by 80 · see citing works
Liu, L., Norman, M. H., Lee, M., Xi, N., Siegmund, A., Boezio, A. A., Booker, S. K., Choquette, D., D’Angelo, N. D., Germain, J., et al. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201331s · Cited by 79 · see citing works
Role of the HGF/c-MET tyrosine kinase inhibitors in metastasic melanoma
Demková, L., & Kučerová, L. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0795-z · Cited by 79 · see citing works
Nelson-Taylor, S. K., Le, A. T., Yoo, M., Schubert, L., Mishall, K. M., Doak, A. E., Varella‐Garcia, M., Tan, A. C., & Doebele, R. C. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0008 · Cited by 77 · see citing works
Targeting the MET gene for the treatment of non-small-cell lung cancer
Gelsomino, F., Facchinetti, F., Haspinger, E. R., Garassino, M. C., Trusolino, L., de Braud, F., & Tiseo, M. (2013) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2013.11.006 · Cited by 77 · see citing works
The potential roles of hepatocyte growth factor (HGF)-MET pathway inhibitors in cancer treatment
Appleman, L. J., Parikh, R. A., Wang, P., Beumer, J. H., & Chu, E. (2014) · OncoTargets and Therapy · doi:10.2147/ott.s40241 · Cited by 75 · see citing works
Liu, L., Shi, H., Liu, Y., Anderson, A. E., Peterson, J. J., Greger, J., Martin, A., & Gilmer, T. M. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0698 · Cited by 74 · see citing works
Li, S., Huang, Q., Liu, Y., Zhang, X., Liu, S., He, C., & Gong, P. (2013) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2013.04.001 · Cited by 74 · see citing works
Delitto, D. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i26.8458 · Cited by 72 · see citing works
Axl inhibitors as novel cancer therapeutic agents
Shen, Y., Chen, X., He, J., Liao, D., & Zu, X. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.02.033 · Cited by 71 · see citing works
MET molecular mechanisms and therapies in lung cancer
Lawrence, R. E., & Salgia, R. (2010) · Cell Adhesion & Migration · doi:10.4161/cam.4.1.10973 · Cited by 70 · see citing works
AXL is an oncotarget in human colorectal cancer
Martinelli, E., Martini, G., Cardone, C., Troiani, T., Liguori, G., Vitagliano, D., Napolitano, S., Morgillo, F., Rinaldi, B., Melillo, R. M., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.3962 · Cited by 66 · see citing works
Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment
Rothenberger, N., & Stabile, L. (2017) · Cancers · doi:10.3390/cancers9040039 · Cited by 60 · see citing works
You, K. S., Yi, Y. W., Cho, J., Park, J., & Seong, Y. (2021) · Pharmaceuticals · doi:10.3390/ph14060589 · Cited by 64 · see citing works
Structural and Molecular Insight into Resistance Mechanisms of First Generation cMET Inhibitors
Collie, G. W., Koh, C. M., O’Neill, D. J., Stubbs, C. J., Khurana, P., Eddershaw, A., Snijder, A., Mauritzson, F., Barlind, L., Dale, I. L., et al. (2019) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.9b00276 · Cited by 61 · see citing works
In the clinic: ongoing clinical trials evaluating c-MET-inhibiting drugs
Sharma, N., & Adjei, A. A. (2011) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758834011423403 · Cited by 63 · see citing works
MerTK inhibition is a novel therapeutic approach for glioblastoma multiforme
Knubel, K. H., Pernu, B. M., Sufit, A., Nelson, S., Pierce, A. M., & Keating, A. K. (2014) · Oncotarget · doi:10.18632/oncotarget.1793 · Cited by 62 · see citing works
HGF/c-Met pathway is one of the mediators of sunitinib-induced tumor cell type-dependent metastasis
Shojaei, F., Simmons, B. H., Lee, J. H., Lappin, P. B., & Christensen, J. G. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.01.026 · Cited by 62 · see citing works
Chen, H.-M., Tsai, C., & Hung, W. (2015) · Oncotarget · doi:10.18632/oncotarget.3613 · Cited by 61 · see citing works
Shi, L., Wu, T.-T., Wang, Z., Xue, J., & Xu, Y. (2014) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2014.07.008 · Cited by 61 · see citing works
Matsumoto, S., Miyamoto, N., Hirayama, T., Oki, H., Okada, K., Tawada, M., Iwata, H., Nakamura, K., Yamasaki, S., Miki, H., et al. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2013.10.028 · Cited by 59 · see citing works
Personalized therapy for hepatocellular carcinoma: Where are we now?
Chan, S. L., Wong, A. M., Lee, K., Wong, N., & Chan, A. K. C. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.02.008 · Cited by 59 · see citing works
RON confers lapatinib resistance in HER2-positive breast cancer cells
Wang, Q., Quan, H., Zhao, J., Xie, C., Wang, L., & Lou, L. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.06.022 · Cited by 58 · see citing works
Targeting Angiogenesis in Renal Cell Carcinoma
Lainakis, G., & Bamias, A. (2008) · Current Cancer Drug Targets · doi:10.2174/156800908785133132 · Cited by 58 · see citing works
Choi, H., Kim, Y., Lee, S., & Kim, Y. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0628 · Cited by 58 · see citing works
Rayson, D., Lupichuk, S., Potvin, K., Dent, S. F., Shenkier, T., Dhesy‐Thind, S., Ellard, S. L., Prady, C. C. M., Salim, M., Farmer, P. L., et al. (2016) · Breast Cancer Research and Treatment · doi:10.1007/s10549-016-3812-1 · Cited by 58 · see citing works
Role of cMET in the Development and Progression of Colorectal Cancer
Pérez-Vargas, J. C. S., Biondani, P., Maggi, C., Gariboldi, M., Gloghini, A., Inno, A., Volpi, C. C., Gualeni, A. V., Bartolomeo, M. D., de Braud, F., et al. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140918056 · Cited by 58 · see citing works
Foretinib is effective therapy for metastatic sonic hedgehog medulloblastoma.
Faria, C., Golbourn, B., Dubuc, A., Remke, M., Diaz, R., Agnihotri, S., Luck, A. J., Sabha, N., Olsen, S., Wu, X.-C., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-13-3629 · Cited by 52 · see citing works
Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs
Heinzlmeir, S., Kudlinzki, D., Sreeramulu, S., Klaeger, S., Gande, S. L., Linhard, V., Wilhelm, M., Qiao, H., Helm, D., Ruprecht, B., et al. (2016) · ACS Chemical Biology · doi:10.1021/acschembio.6b00709 · Cited by 56 · see citing works
Huynh, H. T., Ong, R., & Soo, K. C. (2011) · Angiogenesis · doi:10.1007/s10456-011-9243-z · Cited by 56 · see citing works
Targeting the Hepatocyte Growth Factor/c-Met Signaling Pathway in Renal Cell Carcinoma
Harshman, L. C., & Choueiri, T. K. (2013) · The Cancer Journal · doi:10.1097/ppo.0b013e31829e3c9a · Cited by 55 · see citing works
Ekins, S., Reynolds, R. C., Franzblau, S. G., Wan, B., Freundlich, J. S., & Bunin, B. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063240 · Cited by 55 · see citing works
TSLP Signaling Network Revealed by SILAC-Based Phosphoproteomics
Zhong, J., Kim, M., Chaerkady, R., Wu, X., Huang, T., Getnet, D., Mitchell, C. J., Palapetta, S. M., Sharma, J. N., O’Meally, R. N., et al. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.017764 · Cited by 55 · see citing works
Cheng, P., Phillips, E. S., Kim, S.-H., Taylor, D., Hielscher, T., Puccio, L., Hjelmeland, A. B., Lichter, P., Nakano, I., & Goidts, V. (2015) · Stem Cell Reports · doi:10.1016/j.stemcr.2015.03.005 · Cited by 55 · see citing works
Qi, B., Mi, B., Zhai, X., Xu, Z., Zhang, X., Tian, Z., & Gong, P. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2013.06.026 · Cited by 54 · see citing works
Daouı, O., Elkhattabi, S., Bakhouch, M., Belaıdı, S., Bhandare, R. R., SHAIK, A. B., Mali, S. N., & Chtita, S. (2023) · ACS Omega · doi:10.1021/acsomega.2c07585 · Cited by 53 · see citing works
Cui, P., Yu, M., Peng, X., Dong, L., & Yang, Z.-X. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00933.x · Cited by 53 · see citing works
Butein, a novel dual inhibitor of MET and EGFR, overcomes gefitinib‐resistant lung cancer growth
Jung, S. K., Lee, M., Lim, D. Y., Lee, S., Jeong, C., Kim, J., Lim, T. G., Chen, H., Bode, A. M., Lee, H. J., et al. (2014) · Molecular Carcinogenesis · doi:10.1002/mc.22191 · Cited by 53 · see citing works
Caspase inhibitors: a review of recently patented compounds (2013-2015)
Lee, H., Shin, E. A., Lee, J. H., Ahn, D., Kim, C.-G., Kim, J., & Kim, S. (2017) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2017.1378426 · Cited by 53 · see citing works
- Authors
- Qian, F., Engst, S., Yamaguchi, K., Yu, P., Won, K.-A., Mock, L., Lou, T., Tan, J., Li, C., Tam, D., Lougheed, J., Yakes, F. M., Bentzien, F., Xu, W., Zaks, T., Wooster, R., Greshock, J., & Joly, A. H.
- Affiliations
- Exelixis (United States) (US)
- 1Exelixis, Inc., South San Francisco, California and
- GlaxoSmithKline (United States) (US)
- Venue
- Cancer Research
- Published
- 2009-10-14
- Volume
- 69
- Issue
- 20
- Pages
- 8009-8016
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2130921495
- Cited by
- 350
- References
- 48
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 18 · 2023: 24 · 2022: 14 · 2021: 25 · 2020: 20 · 2019: 12 · 2018: 13 · 2017: 26 · 2016: 17 · 2015: 31 · 2014: 20 · 2013: 44 · 2012: 27
- FWCI
- 8.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- MET receptor tyrosine kinase, hepatocyte growth factor, tyrosine kinase inhibitors, tumor invasion, lung metastasis, angiogenesis, tumor cell proliferation, hypoxia, endothelial cells, KIT, FLT3, PDGFRβ, Tie2
- MeSH terms
- Anilides, Animals, Cell Adhesion, Cell Movement, Cells, Cultured, Endothelium, Vascular, Enzyme-Linked Immunosorbent Assay, Female, Fibroblasts, Humans, Lung Neoplasms, Mice, Inbred BALB C, Mice, Nude, Neoplasm Invasiveness, Neoplasms, Experimental, Neovascularization, Pathologic, Phosphorylation, Quinolines, Umbilical Veins, Blotting, Western, Apoptosis, Hepatocyte Growth Factor, Proto-Oncogene Proteins c-met, Dermis, Receptors, Vascular Endothelial Growth Factor, Protein Kinase Inhibitors, Cell Proliferation, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
