Targeting the cancer kinome through polypharmacology
Open accessAbstract
Kinase inhibitors are the largest class of new cancer drugs. However, it is already apparent that most tumours can escape from the inhibition of any single kinase. If it is necessary to inhibit multiple kinases, how do we choose which ones? In this Opinion article, we discuss some of the strategies that are currently being used to identify new therapeutic combinations of kinase targets.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
No correlation was found between frequency of degradation and maximum observed protein abundance fold change for each kinase, with knowledge metrics such as the pubmed score and the number of entries in the PDB.
“We found no correlation between these variables, consistent with evidence that kinase inhibitor pharmacophores display a high degree of polypharmacology”
From Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development (2020) · cites this paper as Knight et al., 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674 · see citing works
The protein kinase complement of the human genome
Manning, G., Whyte, D. B., Martinez, R., Hunter, T., & Sudarsanam, S. (2002) · Science · doi:10.1126/science.1075762 · Cited by 8,145 · see citing works
Paclitaxel–Carboplatin Alone or with Bevacizumab for Non–Small-Cell Lung Cancer
Sandler, A., Gray, R., Perry, M. C., Brahmer, J., Schiller, J. H., Dowlati, A., Lilenbaum, R., & Johnson, D. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061884 · Cited by 5,761 · see citing works
Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma
Motzer, R. J., Hutson, T. E., Tomczak, P., Michaelson, M. D., Bukowski, R. M., Rixe, O., Oudard, S. M., Négrier, S., Szczylik, C. A., Kim, S. T., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa065044 · Cited by 5,752 · see citing works
Erlotinib in Previously Treated Non–Small-Cell Lung Cancer
Shepherd, F. A., Rodrigues Pereira, J., Ciuleanu, T., Tan, E. H., Hirsh, V., Thongprasert, S., Campos, D., Maoleekoonpiroj, S., Smylie, M., Martins, R., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050753 · Cited by 5,419 · see citing works
Druker, B. J., Talpaz, M., Resta, D. J., Peng, B., Buchdunger, E., Ford, J., Lydon, N., Kantarjian, H. M., Capdeville, R., Ohno-Jones, S., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200104053441401 · Cited by 5,237 · see citing works
Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma
Escudier, B. J., Eisen, T. G., Stadler, W. M., Szczylik, C. A., Oudard, S. M., Siebels, M., Négrier, S., Chevreau, C., Solska, E., Desai, A. A., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa060655 · Cited by 4,802 · see citing works
Network pharmacology: the next paradigm in drug discovery
Hopkins, A. L. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.118 · Cited by 4,622 · 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
Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1
Barbie, D. A., Tamayo, P., Boehm, J. S., Kim, S. Y., Moody, S. E., Dunn, I. F., Schinzel, A. C., Sandy, P., Meylan, E., Scholl, C., et al. (2009) · Nature · doi:10.1038/nature08460 · Cited by 3,869 · see citing works
Moore, M. J., Goldstein, D., Hamm, J., Figer, A., Hecht, J. R., Gallinger, S., Au, H. J., Murawa, P., Walde, D., Wolff, R. A., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.07.9525 · Cited by 3,848 · see citing works
<i>K-ras</i> Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer
Karapetis, C. S., Khambata-Ford, S., Jonker, D. J., O'Callaghan, C. J., Tu, D., Tebbutt, N. C., Simes, R. J., Chalchal, H., Shapiro, J. D., Robitaille, S., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804385 · Cited by 3,622 · see citing works
Pao, W., Miller, V. A., Politi, K. A., Riely, G. J., Somwar, R., Zakowski, M. F., Kris, M. G., & Varmus, H. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020073 · Cited by 3,527 · see citing works
Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia
Druker, B. J., Guilhot, F., O’Brien, S. G., Gathmann, I., Kantarjian, H. M., Gattermann, N., Deininger, M. W., Silver, R. T., Goldman, J. M., Stone, R. M., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa062867 · Cited by 3,474 · see citing works
Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer
Geyer, C. E., Forster, J. K., Lindquist, D. L., Chan, S. Y. T., Romieu, C. G., Pieńkowski, T., Jagiełło-Gruszfeld, A., Crown, J. P., Chan, A., Kaufman, B., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa064320 · Cited by 3,419 · see citing works
Watterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395 · see citing works
Specificity and mechanism of action of some commonly used protein kinase inhibitors.
Davies, S., Reddy, H., Caivano, M., & Cohen, P. (2000) · Biochemical Journal · doi:10.1042/bj3510095 · Cited by 3,164 · see citing works
The Consensus Coding Sequences of Human Breast and Colorectal Cancers
Sjöblom, T., Jones, S., Wood, L. D., Parsons, D. W., Lin, J., Barber, T. D., Mandelker, D. L., Leary, R. J., Ptak, J., Silliman, N., et al. (2006) · Science · doi:10.1126/science.1133427 · Cited by 3,161 · see citing works
Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification
Gorre, M. E., Mohammed, M., Ellwood, K., Hsu, N., Paquette, R., Rao, P. N., & Sawyers, C. L. (2001) · Science · doi:10.1126/science.1062538 · Cited by 3,104 · see citing works
Paclitaxel plus Bevacizumab versus Paclitaxel Alone for Metastatic Breast Cancer
Miller, K. D., Wang, M., Gralow, J. R., Dickler, M. N., Cobleigh, M., Perez, E. A., Shenkier, T. N., Cella, D. F., & Davidson, N. E. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa072113 · Cited by 3,077 · see citing works
Motzer, R. J., Escudier, B., Oudard, S., Hutson, T. E., Porta, C., Bracarda, S., Grünwald, V., Thompson, J. A., Figlin, R. A., Hollaender, N., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61039-9 · Cited by 3,019 · see citing works
The Genomic Landscapes of Human Breast and Colorectal Cancers
Wood, L. D., Parsons, D. W., Jones, S., Lin, J., Sjöblom, T., Leary, R. J., Shen, D., Boca, S. M., Barber, T., Ptak, J., et al. (2007) · Science · doi:10.1126/science.1145720 · Cited by 2,833 · see citing works
Yang, J. C., Haworth, L. R., Sherry, R. M., Hwu, P., Schwartzentruber, D. J., Topalian, S. L., Steinberg, S. M., Chen, H. X., & Rosenberg, S. A. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa021491 · Cited by 2,681 · see citing works
Trastuzumab — Mechanism of Action and Use in Clinical Practice
Hudis, C. A. (2007) · New England Journal of Medicine · doi:10.1056/nejmra043186 · Cited by 2,592 · see citing works
The selectivity of protein kinase inhibitors: a further update
Bain, J., Plater, L., Elliott, M., Shpiro, N., Hastie, C. J., McLauchlan, H., Klevernic, I. V., Arthur, J. S. C., Alessi, D. R., & Cohen, P. (2007) · Biochemical Journal · doi:10.1042/bj20070797 · Cited by 2,522 · see citing works
A quantitative analysis of kinase inhibitor selectivity
Karaman, M. W., Herrgard, S., Treiber, D. K., Gallant, P., Atteridge, C. E., Campbell, B. T., Chan, K. W., Ciceri, P., Davis, M. I., Edeen, P. T., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1358 · Cited by 2,466 · see citing works
Kinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor
Heinrich, M. C., Corless, C. L., Demetri, G. D., Blanke, C. D., von Mehren, M., Joensuu, H., McGreevey, L. S., Chen, C.-J., den Abbeele, A. D. V., Druker, B. J., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.190 · Cited by 2,297 · see citing works
EGFR Antagonists in Cancer Treatment
Ciardiello, F., & Tortora, G. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0707704 · Cited by 2,063 · see citing works
Phosphatidylinositol-3-OH kinase direct target of Ras
Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M. J., Waterfield, M. D., & Downward, J. (1994) · Nature · doi:10.1038/370527a0 · Cited by 1,954 · see citing works
Cetuximab for the Treatment of Colorectal Cancer
Jonker, D. J., O'Callaghan, C. J., Karapetis, C. S., Zalcberg, J. R., Tu, D., Au, H.-J., Berry, S. R., Krahn, M., Price, T., Simes, R. J., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa071834 · Cited by 1,904 · see citing works
A small molecule–kinase interaction map for clinical kinase inhibitors
Fabian, M. A., Biggs, W., Treiber, D. K., Atteridge, C. E., Azimioara, M. D., Benedetti, M. G., Carter, T. A., Ciceri, P., Edeen, P. T., Floyd, M. B., et al. (2005) · Nature Biotechnology · doi:10.1038/nbt1068 · Cited by 1,901 · see citing works
Borst, O., Walker, B., Münzer, P., Russo, A., Schmid, E., Faggio, C., Bigalke, B., Laufer, S., Gawaz, M., & Lang, F. J. W. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350110 · Cited by 1,867 · see citing works
Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias
Talpaz, M., Shah, N. P., Kantarjian, H., Donato, N., Nicoll, J., Paquette, R., Cortes, J., O'Brien, S., Nicaise, C., Bleickardt, E., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055229 · Cited by 1,760 · see citing works
Cools, J., DeAngelo, D. J., Gotlib, J. R., Stover, E. H., Legare, R. D., Cortes, J. E., Kutok, J. L., Clark, J., Galinsky, I. A., Griffin, J. D., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa025217 · Cited by 1,704 · see citing works
Specificity and mechanism of action of some commonly used protein kinase inhibitors
Davies, S., Reddy, H., Caivano, M., & Cohen, P. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3510095 · Cited by 1,618 · see citing works
Cetuximab in the treatment of colorectal cancer.
Goldberg, R. M., Venook, A. P., & Schilsky, R. L. (2004) · PubMed · Cited by 1,518 · see citing works
KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib
Pao, W. J., Wang, T. Y., Riely, G. J., Miller, V. A., Pan, Q., Ladanyi, M., Zakowski, M. F., Heelan, R. T., Kris, M. G., & VARMUS, H. E. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020017 · Cited by 1,517 · see citing works
Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors
Mellinghoff, I. K., Wang, M. Y., Vivanco, I., Haas-Kogan, D. A., Zhu, S., Dia, E. Q., Lu, K. V., Yoshimoto, K., Huang, J. H. Y., Chute, D. J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051918 · Cited by 1,442 · 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
Nilotinib in Imatinib-Resistant CML and Philadelphia Chromosome–Positive ALL
Kantarjian, H. M., Giles, F. J., Wunderle, L., Bhalla, K. N., O'Brien, S. M., Waßmann, B., Tanaka, C., Manley, P. W., Rae, P., Mietlowski, W. L., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055104 · Cited by 1,334 · see citing works
Engelman, J. A., Chen, L., Tan, X., Crosby, K., Guimaraes, A. R., Upadhyay, R., Maira, M., McNamara, K., Perera, S. A., Song, Y., et al. (2008) · Nature Medicine · doi:10.1038/nm.1890 · Cited by 1,330 · see citing works
Chemotherapy, Bevacizumab, and Cetuximab in Metastatic Colorectal Cancer
Tol, J., Koopman, M., Cats, A., Rodenburg, C. J., Creemers, G. J., Schrama, J. G., Erdkamp, F., Vos, A. H., van Groeningen, C. J., Sinnige, H. A. M., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808268 · Cited by 1,330 · see citing works
BRAF mutation predicts sensitivity to MEK inhibition
Solit, D. B., Garraway, L. A., Pratilas, C. A., Sawai, A., Getz, G. A., Basso, A., Ye, Q., Lobo, J. M., She, Y., Osman, I., et al. (2005) · Nature · doi:10.1038/nature04304 · Cited by 1,317 · see citing works
O’Hare, T., Shakespeare, W. C., Zhu, X., Eide, C. A., Rivera, V. M., Wang, F., Adrian, L. T., Zhou, T., Huang, W.-S., Xu, Q., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.09.028 · Cited by 1,270 · 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
A Genome-wide RNAi Screen Identifies Multiple Synthetic Lethal Interactions with the Ras Oncogene
Luo, J., Emanuele, M. J., Li, D., Creighton, C. J., Schlabach, M. R., Westbrook, T. F., Wong, K.-K., & Elledge, S. J. (2009) · Cell · doi:10.1016/j.cell.2009.05.006 · Cited by 1,017 · see citing works
Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3
Sergina, N. V., Rausch, M., Wang, D., Blair, J. A., Hann, B. C., Shokat, K. M., & Moasser, M. M. (2007) · Nature · doi:10.1038/nature05474 · Cited by 993 · see citing works
Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies
Stommel, J. M., Kimmelman, A. C., Ying, H., Nabioullin, R., Ponugoti, A. H., Wiedemeyer, R., Stegh, A. H., Bradner, J. E., Ligon, K. L., Brennan, C., et al. (2007) · Science · doi:10.1126/science.1142946 · Cited by 938 · see citing works
Mutant PIK3CA promotes cell growth and invasion of human cancer cells.
Samuels, Y., Diaz, L. A., Schmidt-Kittler, O., Cummins, J. M., DeLong, L., Cheong, I., Rago, C., Huso, D. L., Lengauer, C., Kinzler, K. W., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.05.014 · Cited by 915 · see citing works
Junttila, T. T., Akita, R. W., Parsons, K. L., Fields, C. T., Phillips, G. D. L., Friedman, L. S., Sampath, D., & Sliwkowski, M. X. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.020 · Cited by 829 · see citing works
Features of Selective Kinase Inhibitors
Knight, Z. A., & Shokat, K. M. (2005) · Chemistry & Biology · doi:10.1016/j.chembiol.2005.04.011 · Cited by 663 · see citing works
Haigis, K. M., Kendall, K. R., Wang, Y., Cheung, A., Haigis, M. C., Glickman, J. N., Niwa-Kawakita, M., Sweet-Cordero, A., Sebolt-Leopold, J., Shannon, K. M., et al. (2008) · Nature Genetics · doi:10.1038/ng.115 · Cited by 610 · see citing works
Mutations in a signalling pathway
Parsons, D. W., Wang, T., Samuels, Y., Bardelli, A., Cummins, J. M., Wood, L. D., Silliman, N., Ptak, J., Szabo, S., Willson, J. K. V., et al. (2005) · Nature · doi:10.1038/436792a · Cited by 599 · see citing works
Binding of Ras to Phosphoinositide 3-Kinase p110α Is Required for Ras- Driven Tumorigenesis in Mice
Gupta, S., Ramjaun, A. R., Haiko, P., Wang, Y., Warne, P. H., Nicke, B., Nye, E. L., Stamp, G., Alitalo, K. K., & Downward, J. (2007) · Cell · doi:10.1016/j.cell.2007.03.051 · Cited by 589 · see citing works
A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma
Fan, Q.-W., Knight, Z. A., Goldenberg, D., Yu, W., Mostov, K. E., Stokoe, D., Shokat, K. M., & Weiss, W. A. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.029 · Cited by 584 · see citing works
Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases
Carter, T. A., Wodicka, L. M., Shah, N. P., Velasco, A. M., Fabian, M. A., Treiber, D. K., Milanov, Z. V., Atteridge, C. E., Biggs, W., Edeen, P. T., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504952102 · Cited by 550 · see citing works
Hauschild, A., Agarwala, S. S., Trefzer, U., Hogg, D., Robert, C., Hersey, P., Eggermont, A. M. M., Grabbe, S., Gonzalez, R. C., Gille, J., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.7636 · Cited by 548 · see citing works
Moulder, S. L., Yakes, F. M., Muthuswamy, S. K., Bianco, R., Simpson, J. F., & Arteaga, C. L. (2001) · PubMed · Cited by 548 · see citing works
Scholl, C., Fröhling, S., Dunn, I. F., Schinzel, A. C., Barbie, D. A., Kim, S. Y., Silver, S. J., Tamayo, P., Wadlow, R. C., Ramaswamy, S., et al. (2009) · Cell · doi:10.1016/j.cell.2009.03.017 · Cited by 539 · see citing works
Requirement for NF-κB signalling in a mouse model of lung adenocarcinoma
Meylan, E., Dooley, A. L., Feldser, D. M., Shen, L., Turk, E., Ouyang, C., & Jacks, T. (2009) · Nature · doi:10.1038/nature08462 · Cited by 514 · see citing works
Eichhorn, P. J. A., Gili, M., Scaltriti, M., Serra, V., Guzman, M., Nijkamp, W., Beijersbergen, R. L., Valero, V., Seoane, J., Bernards, R., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1740 · Cited by 499 · see citing works
Can we rationally design promiscuous drugs?
HOPKINS, A., MASON, J., & OVERINGTON, J. (2006) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2006.01.013 · Cited by 469 · see citing works
PI3K Pathway Activation Mediates Resistance to MEK Inhibitors in KRAS Mutant Cancers
Wee, S., Jagani, Z., Xiang, K. X., Loo, A., Dorsch, M., Yao, Y.-M., Sellers, W. R., Lengauer, C., & Stegmeier, F. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4765 · Cited by 455 · see citing works
Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases
Apsel, B., Blair, J. A., González, B., Nazif, T. M., Feldman, M. E., Aizenstein, B., Hoffman, R., Williams, R. L., Shokat, K. M., & Knight, Z. A. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.117 · Cited by 452 · see citing works
Discovery of a novel Raf kinase inhibitor.
Lyons, J. F., Wilhelm, S. M., Hibner, B., & Bollag, G. E. (2001) · Endocrine Related Cancer · doi:10.1677/erc.0.0080219 · Cited by 415 · see citing works
Shah, N. P., Skaggs, B. J., Branford, S., Hughes, T. P., Nicoll, J. M., PAQUETTE, R. L., & Sawyers, C. L. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30890 · Cited by 409 · see citing works
Giles, F. J., Cortes, J. E., Jones, D. M., Bergstrom, D. A., Kantarjian, H. M., & Freedman, S. J. (2006) · Blood · doi:10.1182/blood-2006-05-025049 · Cited by 361 · see citing works
A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases
Fedorov, O., Marsden, B. D., Pogačić, V., Rellos, P., Müller, S., Bullock, A. N., Schwaller, J., Sundström, M., & Knapp, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708800104 · Cited by 361 · see citing works
McDermott, U., Sharma, S. V., Dowell, L., Greninger, P., Montagut, C. O., Lamb, J. A., Archibald, H., Raudales, R., Tam, A., Lee, D. W., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707498104 · Cited by 352 · see citing works
Chen, L. L., Trent, J. C., Wu, E. F., Fuller, G. N., Ramdas, L., Zhang, W., Raymond, A. K., Prieto, V. G., Oyedeji, C. O., Hunt, K. K., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0085 · Cited by 339 · see citing works
Tamborini, E., Bonadiman, L., Greco, A., Albertini, V., Negri, T., Gronchi, A., Bertulli, R., Colecchia, M., Casali, P. G., Pierotti, M. A., et al. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.02.021 · Cited by 323 · see citing works
Bukowski, R. M., Kabbinavar, F. F., Figlin, R. A., Flaherty, K. T., Srinivas, S., Vaishampayan, U. N., Drabkin, H. A., Dutcher, J. P., Ryba, S., Xia, Q., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.11.5154 · Cited by 314 · see citing works
Treatment of hypereosinophilic syndrome with imatinib mesilate
Gleich, G. J., Leiferman, K. M., Pardanani, A. D., Tefferi, A., & Butterfield, J. H. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08505-7 · Cited by 303 · see citing works
Renewing the conspiracy theory debate: does Raf function alone to mediate Ras oncogenesis?
Repasky, G. A., Chenette, E. J., & Der, C. J. (2004) · Trends in Cell Biology · doi:10.1016/j.tcb.2004.09.014 · Cited by 299 · see citing works
Normanno, N., Campiglio, M., Luca, A. D., Somenzi, G., Maiello, M. R., Ciardiello, F., Gianni, L., Salomon, D. S., & Ménard, S. (2002) · Annals of Oncology · doi:10.1093/annonc/mdf020 · Cited by 273 · see citing works
Chemical Genetics: Where Genetics and Pharmacology Meet
Knight, Z. A., & Shokat, K. M. (2007) · Cell · doi:10.1016/j.cell.2007.01.021 · Cited by 244 · see citing works
Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo
Luo, Y., Shoemaker, A. R., Liu, X., Woods, K. W., Thomas, S. A., de Jong, R., Han, E. K.-H., Li, T., Stoll, V. S., Powlas, J. A., et al. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0005 · Cited by 233 · see citing works
Shah, N. P., Kasap, C., Weier, C. A., Balbas, M., Nicoll, J. M., Bleickardt, E. W., Nicaise, C., & Sawyers, C. L. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.11.001 · Cited by 231 · see citing works
Use of isogenic human cancer cells for high-throughput screening and drug discovery
Torrance, C. J., Agrawal, V., Vogelstein, B., & Kinzler, K. W. (2001) · Nature Biotechnology · doi:10.1038/nbt1001-940 · Cited by 228 · see citing works
Fan, Q.-W., Cheng, C. K., Nicolaides, T. P., Hackett, C. S., Knight, Z. A., Shokat, K. M., & Weiss, W. A. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2154 · Cited by 193 · see citing works
Target Identification in Chemical Genetics
Burdine, L. J., & Kodadek, T. J. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.05.001 · Cited by 191 · see citing works
Gontarewicz, A., Balabanov, S., Keller, G., Colombo, R., Graziano, A., Pesenti, E. A., Benten, D., Bokemeyer, C., Fiedler, W., Moll, J. K., et al. (2008) · Blood · doi:10.1182/blood-2007-09-113175 · Cited by 166 · see citing works
Assessment of Chemical Coverage of Kinome Space and Its Implications for Kinase Drug Discovery
Bamborough, P., Drewry, D. H., Harper, G., Smith, G. K., & Schneider, K. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm8011036 · Cited by 162 · see citing works
Tonra, J. R., Deevi, D. S., Corcoran, E., Li, H., Wang, S., Carrick, F. E., & Hicklin, D. J. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1682 · Cited by 148 · see citing works
Weinstein, I. B., Begemann, M., Zhou, P., Han, E. K.-H., Sgambato, A., Doki, Y., Arber, N., Ciaparrone, M., & Yamamoto, H. (1997) · PubMed · Cited by 125 · see citing works
Motwani, M., Jung, C. P., Sirotnak, F. M., She, Y., Shah, M. A., Gönen, M., & Schwartz, G. K. (2001) · PubMed · Cited by 117 · see citing works
Akritopoulou‐Zanze, I., & Hajduk, P. J. (2009) · Drug Discovery Today · doi:10.1016/j.drudis.2008.12.002 · Cited by 116 · see citing works
Strumberg, D., Voliotis, D., Moeller, J.-G., Hilger, R. A., Richly, H., Kredtke, S., Beling, C., Scheulen, M. E., & Seeber, S. (2002) · International Journal of Clinical Pharmacology and Therapeutics · doi:10.5414/cpp40580 · Cited by 104 · see citing works
A Phase I Clinical Trial of the Sequential Combination of Irinotecan Followed by Flavopiridol
Shah, M. A., Kortmansky, J. S., Motwani, M., Drobnjak, M., Gönen, M., Yi, S., Weyerbacher, A. R., Cordon‐Cardo, C., Lefkowitz, R. A., Brenner, B., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-2651 · Cited by 101 · see citing works
Kinase requirements in human cells: I. Comparing kinase requirements across various cell types
Grueneberg, D. A., Degot, S., Pearlberg, J., Li, W., Davies, J. E., Baldwin, A. E., Endege, W. O., Doench, J. G., Sawyer, J., Hu, Y., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808019105 · Cited by 88 · see citing works
Warburton, C., Dragowska, W. H., Gelmon, K. A., Chia, S., Yan, H., Masin, D., Denyssevych, T., Wallis, A. E., & Bally, M. B. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-03-0244 · Cited by 83 · see citing works
O’Hare, T., Eide, C. A., Tyner, J. W., Corbin, A. S., Wong, M. J., Buchanan, S. G., Holme, K. R., Jessen, K. A., Tang, C. M., Lewis, H. A., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800587105 · Cited by 80 · see citing works
Arteaga, C. L., O’Neill, A., Moulder, S. L., Pins, M., Sparano, J. A., Sledge, G. W., & Davidson, N. E. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0482 · Cited by 79 · see citing works
Challenges and Opportunities in Defining the Essential Cancer Kinome
Manning, B. D. (2009) · Science Signaling · doi:10.1126/scisignal.263pe15 · Cited by 59 · see citing works
Sawyers, C. L. (2007) · Nature · doi:10.1038/449993a · Cited by 59 · see citing works
Morgan-Lappe, S. E., Woods, K. W., Li, Q., Anderson, M. G., Schurdak, M. E., Luo, Y., Giranda, V. L., Fesik, S. W., & Leverson, J. D. (2005) · Oncogene · doi:10.1038/sj.onc.1209169 · Cited by 53 · see citing works
Baldwin, A. E., Li, W., Grace, M. R., Pearlberg, J., Harlow, E., Münger, K., & Grueneberg, D. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806195105 · Cited by 46 · see citing works
For Investigational Targeted Drugs, Combination Trials Pose Challenges
Goldman, B. (2003) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/95.23.1744 · Cited by 15 · see citing works
Is the gefitinib plus trastuzumab combination feasible in breast cancer patients?
Normanno, N., Campiglio, M., Perrone, F., Luca, A. D., & Ménard, S. (2005) · Annals of Oncology · doi:10.1093/annonc/mdi325 · Cited by 11 · see citing works
History and Accomplishments of the Inter-Company Collaboration for Aids Drug Development
Barry, D. W., & Distlerath, L. M. (2000) · Drug Information Journal · doi:10.1177/009286150003400310 · Cited by 3 · see citing works
Optimising strategies for clinical development of combinations of targeted agents
Chen, H. (2007) · European Journal of Cancer Supplements · doi:10.1016/j.ejcsup.2007.09.030 · Cited by 1 · see citing works
Flagged first, then by citations
3 of the 104 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Comprehensive analysis of kinase inhibitor selectivity
Davis, M. I., Hunt, J. P., Herrgard, S., Ciceri, P., Wodicka, L. M., Pallares, G., Hocker, M., Treiber, D. K., & Zarrinkar, P. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1990 · Cited by 2,409 · see citing works
The ErbB/HER family of protein-tyrosine kinases and cancer
Roskoski, R. J. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.11.002 · Cited by 1,365 · see citing works
Kinase-targeted cancer therapies: progress, challenges and future directions
Bhullar, K. S., Orrego-Lagarón, N., McGowan, E. M., Parmar, I., Jha, A., Hubbard, B. P., & Rupasinghe, H. P. V. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0804-2 · Cited by 1,260 · see citing works
Target identification and mechanism of action in chemical biology and drug discovery
Schenone, M., Dančík, V., Wagner, B. K., & Clemons, P. A. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1199 · Cited by 1,107 · see citing works
Polypharmacology: Challenges and Opportunities in Drug Discovery: Miniperspective
Anighoro, A., Bajorath, J., & Rastelli, G. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5006463 · Cited by 1,131 · see citing works
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity
Anastassiadis, T., Deacon, S. W., Devarajan, K., Ma, H., & Peterson, J. R. (2011) · Nature Biotechnology · doi:10.1038/nbt.2017 · Cited by 919 · see citing works
Automated design of ligands to polypharmacological profiles
Besnard, J., Ruda, G. F., Setola, V., Abecassis, K., Rodriguiz, R. M., Huang, X.-P., Norval, S., Sassano, M. F., Shin, A. I., Webster, L. A., et al. (2012) · Nature · doi:10.1038/nature11691 · Cited by 832 · see citing works
Franken, H., Mathieson, T., Childs, D., Sweetman, G. M. A., Werner, T., Tögel, I., Doce, C., Gade, S., Bantscheff, M., Drewes, G., et al. (2015) · Nature Protocols · doi:10.1038/nprot.2015.101 · Cited by 638 · see citing works
Tang, J. P., Szwajda, A., Shakyawar, S. K., Xu, T., Hintsanen, P., Wennerberg, K., & Aittokallio, T. A. (2014) · Journal of Chemical Information and Modeling · doi:10.1021/ci400709d · Cited by 664 · see citing works
Gelbert, L. M., Cai, S., Lin, X., Sanchez-Martinez, C., del Prado, M., Lallena, M. J., Torres, R., Ajamie, R. T., Wishart, G. N., Flack, R. S., et al. (2014) · Investigational New Drugs · doi:10.1007/s10637-014-0120-7 · Cited by 577 · see citing works
Multiplexed mass cytometry profiling of cellular states perturbed by small-molecule regulators
Bodenmiller, B., Zunder, E. R., Finck, R., Chen, T. J., Savig, E. S., Bruggner, R. V., Simonds, E. F., Bendall, S. C., Sachs, K., Krutzik, P. O., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2317 · Cited by 546 · see citing works
SynergyFinder: a web application for analyzing drug combination dose–response matrix data
Ianevski, A., He, L., Aittokallio, T. A., & Tang, J. P. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx162 · Cited by 535 · see citing works
Polypharmacology by Design: A Medicinal Chemist’s Perspective on Multitargeting Compounds
Proschak, E., Stark, H., & Merk, D. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00760 · Cited by 498 · see citing works
Polypharmacology – Foe or Friend?
Peters, J. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400856t · Cited by 477 · see citing works
Drug combination therapy increases successful drug repositioning
Sun, W., Sanderson, P. E. J., & Zheng, W. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2016.05.015 · Cited by 438 · see citing works
Drugging the undruggables: exploring the ubiquitin system for drug development
Huang, X., & Dixit, V. M. (2016) · Cell Research · doi:10.1038/cr.2016.31 · Cited by 427 · see citing works
Advances in sarcoma genomics and new therapeutic targets
Taylor, B. S., Barretina, J. G., Maki, R. G., Antonescu, C. R., Singer, S., & Ladanyi, M. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3087 · Cited by 428 · see citing works
FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR
Bivona, T. G., Hieronymus, H., Parker, J., Chang, K., Taron, M., Rosell, R., Moonsamy, P., Dahlman, K., Miller, V. A., Costa, C., et al. (2011) · Nature · doi:10.1038/nature09870 · Cited by 396 · see citing works
The Evolution of Protein Kinase Inhibitors from Antagonists to Agonists of Cellular Signaling
Dar, A. C., & Shokat, K. M. (2011) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-090308-173656 · Cited by 388 · see citing works
Anticancer drug resistance: An update and perspective
Nussinov, R., Tsai, C., & Jang, H. (2021) · Drug Resistance Updates · doi:10.1016/j.drup.2021.100796 · Cited by 395 · see citing works
Network‐based Approaches in Pharmacology
Boezio, B., Audouze, K., Ducrot, P., & Taboureau, O. (2017) · Molecular Informatics · doi:10.1002/minf.201700048 · Cited by 364 · see citing works
Redox Signaling by Reactive Electrophiles and Oxidants
Parvez, S., Long, M. J. C., Poganik, J. R., & Aye, Y. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00698 · Cited by 357 · see citing works
Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development
Donovan, K. A., Ferguson, F. M., Bushman, J. W., Eleuteri, N. A., Bhunia, D., Ryu, S., Tan, L., Shi, K., Yue, H., Liu, X., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.038 · Cited by 359 · see citing works
Targeting Cyclin-Dependent Kinases in Human Cancers: From Small Molecules to Peptide Inhibitors
Peyressatre, M., Prével, C., Pellerano, M., & Morris, M. C. (2015) · Cancers · doi:10.3390/cancers7010179 · Cited by 345 · see citing works
Drug resistance in metastatic castration-resistant prostate cancer
Šeruga, B., Ocaña, A., & Tannock, I. F. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.136 · Cited by 337 · see citing works
Dual or multi-targeting inhibitors: The next generation anticancer agents
Raghavendra, N. M., Pingili, D., Kadasi, S., Mettu, A., & Prasad, S. V. U. M. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.10.021 · Cited by 333 · see citing works
SCF ubiquitin ligase-targeted therapies
Skaar, J. R., Pagan, J. K., & Pagano, M. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4432 · Cited by 336 · see citing works
Chemical genetic discovery of targets and anti-targets for cancer polypharmacology
Dar, A. C., Das, T. K., Shokat, K. M., & Cagan, R. L. (2012) · Nature · doi:10.1038/nature11127 · Cited by 334 · see citing works
Activation pathway of Src kinase reveals intermediate states as targets for drug design
Shukla, D., Meng, Y., Roux, B., & Pande, V. S. (2014) · Nature Communications · doi:10.1038/ncomms4397 · Cited by 333 · see citing works
Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunitiesPreprint
Rambow, F., Marine, J., & Goding, C. R. (2019) · Genes & Development · doi:10.1101/gad.329771.119 · Cited by 316 · see citing works
Review of therapeutic drug monitoring of anticancer drugs part two – Targeted therapies
Widmer, N., Bardin, C., Chatelut, É., Paci, A., Beijnen, J. H., Levêque, D., Veal, G. J., & Astier, A. (2014) · European Journal of Cancer · doi:10.1016/j.ejca.2014.04.015 · Cited by 299 · see citing works
The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase
Sciacovelli, M., Guzzo, G., Morello, V., Frezza, C., Zheng, L., Nannini, N., Calabrese, F., Laudiero, G., Esposito, F., Landriscina, M., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.019 · Cited by 269 · see citing works
Active-learning strategies in computer-assisted drug discovery
Reker, D., & Schneider, G. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.12.004 · Cited by 262 · see citing works
Hunter, J. C., Gurbani, D., Ficarro, S. B., Carrasco, M. A., Lim, S. M., Choi, H. G., Xie, T., Marto, J. A., Chen, Z., Gray, N. S., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1404639111 · Cited by 242 · see citing works
Botanical Drugs, Synergy, and Network Pharmacology: Forth and Back to Intelligent Mixtures
Gertsch, J. (2011) · Planta Medica · doi:10.1055/s-0030-1270904 · Cited by 251 · see citing works
Bekerman, E., Neveu, G., Shulla, A., Brannan, J. M., Pu, S., Wang, S., Xiao, F., Barouch‐Bentov, R., Bakken, R. R., Mateo, R., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci89857 · Cited by 231 · see citing works
Targeting tumour-supportive cellular machineries in anticancer drug development
Dobbelstein, M., & Moll, U. M. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4201 · Cited by 229 · see citing works
Dual Inhibitors of Human DNA Topoisomerase II and Other Cancer-Related Targets
Skok, Ž., Zidar, N., Kikelj, D., & Ilaš, J. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00726 · Cited by 226 · see citing works
Autophagy in the physiological endometrium and cancer
Devis, L., Eritja, N., Davis, M. L., Matías‐Guiu, X., & Llobet‐Navàs, D. (2020) · Autophagy · doi:10.1080/15548627.2020.1752548 · Cited by 226 · see citing works
Fan, F., Liu, P., Bao, R., Chen, J., Zhou, M., Mo, Z., Ma, Y., Liu, H., Zhou, Y., Cai, X., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-1547 · Cited by 213 · see citing works
Medicinal chemistry strategies for discovering antivirals effective against drug-resistant viruses
Ma, Y., Frutos-Beltrán, E., Kang, D., Pannecouque, C. C., Clercq, E. D., Menéndez‐Arias, L., Liu, X., & Zhan, P. (2021) · Chemical Society Reviews · doi:10.1039/d0cs01084g · Cited by 208 · see citing works
Chromosomal instability and aneuploidy in cancer: from yeast to man
Pfau, S. J., & Amon, A. (2012) · EMBO Reports · doi:10.1038/embor.2012.65 · Cited by 201 · see citing works
Progress with covalent small-molecule kinase inhibitors
Zhao, Z., & Bourne, P. E. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.01.035 · Cited by 200 · see citing works
Xie, L., Xie, L., Kinnings, S., & Bourne, P. E. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134630 · Cited by 198 · see citing works
Fang, Z., Grütter, C., & Rauh, D. (2013) · ACS Chemical Biology · doi:10.1021/cb300663j · Cited by 197 · see citing works
Inhibition of KRAS -Driven Tumorigenicity by Interruption of an Autocrine Cytokine Circuit
Zhu, Z., Aref, A. R., Cohoon, T. J., Barbie, T. U., Imamura, Y., Yang, S., Moody, S. E., Shen, R. R., Schinzel, A. C., Thai, T. C., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0646 · Cited by 193 · see citing works
Modern Phenotypic Drug Discovery Is a Viable, Neoclassic Pharma Strategy
Lee, J. A., Uhlik, M. T., Moxham, C. M., Tomandl, D., & Sall, D. J. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201649s · Cited by 190 · see citing works
Mechanisms of drug resistance in kinases
Barouch‐Bentov, R., & Sauer, K. (2011) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2011.546344 · Cited by 187 · see citing works
Computational Multitarget Drug Design
Zhang, W., Pei, J., & Lai, L. (2017) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.6b00491 · Cited by 186 · see citing works
How Chemoproteomics Can Enable Drug Discovery and Development
Moellering, R. E., & Cravatt, B. F. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.01.001 · Cited by 182 · see citing works
Gowda, H., & Pandey, A. (2010) · Molecular Oncology · doi:10.1016/j.molonc.2010.09.004 · Cited by 177 · see citing works
Discovery and development of natural product oridonin-inspired anticancer agents
Ding, Y., Ding, C., Ye, N., Liu, Z., Wold, E. A., Chen, H., Wild, C., Shen, Q., & Zhou, J. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.06.015 · Cited by 178 · see citing works
Tang, J. P., & Aittokallio, T. A. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113199990470 · Cited by 184 · see citing works
Taking aim at Mer and Axl receptor tyrosine kinases as novel therapeutic targets in solid tumors
Linger, R. M. A., Keating, A. K., Earp, H. S., & Graham, D. K. (2010) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2010.515980 · Cited by 167 · see citing works
Xie, L., Evangelidis, T., Xie, L., & Bourne, P. E. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002037 · Cited by 163 · see citing works
Structure-based systems biology for analyzing off-target binding
Xie, L., Xie, L., & Bourne, P. E. (2011) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2011.01.004 · Cited by 152 · see citing works
Induction of Antagonistic Soluble Decoy Receptor Tyrosine Kinases by Intronic PolyA Activation
Vorlová, S., Rocco, G., LeFave, C. V., Jodelka, F. M., Hess, K. C., Hastings, M. L., Henke, E., & Cartegni, L. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.08.009 · Cited by 142 · see citing works
Lin, A., Giuliano, C. J., Sayles, N. M., & Sheltzer, J. M. (2017) · eLife · doi:10.7554/elife.24179 · Cited by 144 · see citing works
Compound promiscuity: what can we learn from current data?
Hu, Y., & Bajorath, J. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2013.03.002 · Cited by 142 · see citing works
The Landscape of Atypical and Eukaryotic Protein Kinases
Kanev, G. K., de Graaf, C., de Esch, I. J. P., Leurs, R., Würdinger, T., Westerman, B. A., & Kooistra, A. J. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.09.002 · Cited by 143 · see citing works
Espinosa-García, A. M., Alfaro, A., Román-Basaure, E., Guardado-Estrada, M., Lara, I. P., Serralde, C., Medina, I., Juárez, E., Bermúdez, M., Márquez, E., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055975 · Cited by 140 · see citing works
Waibel, M., Solomon, V. S., Knight, D. A., Ralli, R., Kim, S., Banks, K.-M., Vidacs, E., Virely, C., Sia, K. C. S., Bracken, L. S., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.10.038 · Cited by 138 · see citing works
Towards novel paradigms for cancer therapy
Pavet, V., Portal, M. M., Moulin, J.-F., Herbrecht, R., & Gronemeyer, H. (2010) · Oncogene · doi:10.1038/onc.2010.460 · Cited by 132 · see citing works
Neoclassic Drug Discovery: The Case for Lead Generation Using Phenotypic and Functional Approaches
Lee, J. A., & Berg, E. L. (2013) · SLAS DISCOVERY · doi:10.1177/1087057113506118 · Cited by 125 · see citing works
Gao, Y., Davies, S. P., Augustin, M. A., Woodward, A. M., Patel, U. A., Kovelman, R., & Harvey, K. J. (2013) · Biochemical Journal · doi:10.1042/bj20121418 · Cited by 126 · see citing works
Cichońska, A., Ravikumar, B., Parri, E., Timonen, S., Pahikkala, T., Airola, A., Wennerberg, K., Rousu, J., & Aittokallio, T. A. (2017) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1005678 · Cited by 122 · see citing works
Epigenetic polypharmacology: A new frontier for epi‐drug discovery
Tomaselli, D., Lucidi, A., Rotili, D., & Mai, A. (2019) · Medicinal Research Reviews · doi:10.1002/med.21600 · Cited by 126 · see citing works
Draghiciu, O., Nijman, H. W., Hoogeboom, B. N., Meijerhof, T., & Daemen, T. (2015) · OncoImmunology · doi:10.4161/2162402x.2014.989764 · Cited by 123 · see citing works
Targeting apoptosis pathways in cancer stem cells
Signore, M., Ricci‐Vitiani, L., & Maria, R. D. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.01.013 · Cited by 123 · see citing works
The Small Molecules AZD0530 and Dasatinib Inhibit Dengue Virus RNA Replication via Fyn Kinase
de Wispelaere, M., LaCroix, A. J., & Yang, P. L. (2013) · Journal of Virology · doi:10.1128/jvi.00632-13 · Cited by 122 · see citing works
Anthelmintic Drug Discovery: Into the Future
Geary, T. G., Sakanari, J. A., & Caffrey, C. R. (2015) · Journal of Parasitology · doi:10.1645/14-703.1 · Cited by 122 · see citing works
Targeting Mutant KRAS for Anticancer Therapeutics: A Review of Novel Small Molecule Modulators
Wang, Y., Kaiser, C. E., Frett, B., & Li, H. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm3017706 · Cited by 121 · see citing works
Li, Y., Tan, C., Gao, C., Zhang, C., Luan, X., Chen, X., Liu, H., Chen, Y., & Jiang, Y. (2011) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2011.06.022 · Cited by 120 · see citing works
Mallick, A., More, P. A., Ghosh, S., Chippalkatti, R., Chopade, B. A., Lahiri, M., & Basu, S. (2015) · ACS Applied Materials & Interfaces · doi:10.1021/am5090226 · Cited by 119 · see citing works
The role of fragment-based and computational methods in polypharmacology
Bottegoni, G., Favia, A. D., Recanatini, M., & Cavalli, A. (2011) · Drug Discovery Today · doi:10.1016/j.drudis.2011.08.002 · Cited by 116 · see citing works
Quercetin inhibits a large panel of kinases implicated in cancer cell biology
Kiss (2010) · International Journal of Oncology · doi:10.3892/ijo.2010.890 · Cited by 116 · see citing works
Bistrović, A., Krstulović, L., Harej, A., Grbčić, P., Sedić, M., Koštrun, S., Pavelić, S. K., Bajić, M., & Raić‐Malić, S. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.10.061 · Cited by 115 · see citing works
Challenges and Opportunities in the Development of Protein Phosphatase-Directed Therapeutics
Munter, S. D., Köhn, M., & Bollen, M. (2012) · ACS Chemical Biology · doi:10.1021/cb300597g · Cited by 114 · see citing works
Blueprint for cancer research: Critical gaps and opportunities
Elmore, L. W., Greer, S. F., Daniels, E. C., Saxe, C. C., Melner, M. H., Krawiec, G. M., Cance, W. G., & Phelps, W. C. (2020) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21652 · Cited by 121 · see citing works
Abdellatif, K. R. A., & Bakr, R. B. (2020) · Medicinal Chemistry Research · doi:10.1007/s00044-020-02656-8 · Cited by 111 · see citing works
Cheng, F., Jia, P., Wang, Q., & Zhao, Z. (2014) · Oncotarget · doi:10.18632/oncotarget.1984 · Cited by 105 · see citing works
Deciphering UV‐induced DNA Damage Responses to Prevent and Treat Skin Cancer
Lee, J. W., Ratnakumar, K., Hung, K., Rokunohe, D., & Kawasumi, M. (2020) · Photochemistry and Photobiology · doi:10.1111/php.13245 · Cited by 112 · see citing works
New Electrophiles and Strategies for Mechanism-Based and Targeted Covalent Inhibitor Design
Ray, S., & Murkin, A. S. (2019) · Biochemistry · doi:10.1021/acs.biochem.9b00293 · Cited by 108 · see citing works
Cai, J., Sun, M., Wu, X., Chen, J., Wang, P., Zong, X., & Ji, M. (2013) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2013.03.013 · Cited by 105 · see citing works
Polypharmacology in Drug Discovery: A Review from Systems Pharmacology Perspective
Zhang, W., Bai, Y., Wang, Y., & Xiao, W. (2016) · Current Pharmaceutical Design · doi:10.2174/1381612822666160224142812 · Cited by 105 · see citing works
ChemProt: a disease chemical biology database
Taboureau, O., Nielsen, S. K., Audouze, K., Weinhold, N., Edsgärd, D., Roque, F. S., Kouskoumvekaki, I. A., Bora, A., Curpan, R. F., Jensen, T. S., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq906 · Cited by 105 · see citing works
INKA, an integrative data analysis pipeline for phosphoproteomic inference of active kinases
Beekhof, R., van Alphen, C., Henneman, A. A., Knol, J. C., Pham, T. V., Rolfs, F., Labots, M., Henneberry, E., Le Large, T. Y., de Haas, R. R., et al. (2019) · Molecular Systems Biology · doi:10.15252/msb.20188250 · Cited by 97 · see citing works
Uitdehaag, J. C. M., de Roos, J. A. D. M., van Doornmalen, A. M., Prinsen, M. B. W., de Man, J., Tanizawa, Y., Kawase, Y., Yoshino, K., Buijsman, R. C., & Zaman, G. J. R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092146 · Cited by 105 · see citing works
Polypharmacology: The Rise of Multitarget Drugs over Combination Therapies
Rosini, M. (2014) · Future Medicinal Chemistry · doi:10.4155/fmc.14.25 · Cited by 103 · see citing works
Prediction of Chemical-Protein Interactions Network with Weighted Network-Based Inference Method
Cheng, F., Zhou, Y., Li, W., Liu, G., & Tang, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041064 · Cited by 100 · see citing works
Zhang, K., Lai, F., Lin, S., Ji, M., Zhang, J., Zhang, Y., Jin, J., Fu, R., Wu, D., Tian, H., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00390 · Cited by 99 · see citing works
Polypharmacology-based ceritinib repurposing using integrated functional proteomics
Kuenzi, B. M., Rix, L. L. R., Stewart, P. A., Fang, B., Kinose, F., Bryant, A. T., Boyle, T. A., Koomen, J. M., Haura, E. B., & Rix, U. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2489 · Cited by 98 · see citing works
Systems-pharmacology dissection of a drug synergy in imatinib-resistant CML
Winter, G. E., Rix, U., Carlson, S. M., Gleixner, K. V., Grebien, F., Gridling, M., Müller, A. C., Breitwieser, F. P., Bilban, M., Colinge, J., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1085 · Cited by 97 · see citing works
Hauser, K., Negron, C., Albanese, S. K., Ray, S. S., Steinbrecher, T. B., Abel, R., Chodera, J. D., & Wang, L. (2018) · Communications Biology · doi:10.1038/s42003-018-0075-x · Cited by 91 · see citing works
Zheng, P., Li, J., & Kros, J. M. (2017) · Medicinal Research Reviews · doi:10.1002/med.21463 · Cited by 97 · see citing works
De novo generation of multi-target compounds using deep generative chemistry
Munson, B. P., Chen, M., Bogosian, A., Kreisberg, J. F., Licon, K., Abagyan, R. A., Kuenzi, B. M., & Ideker, T. E. (2024) · Nature Communications · doi:10.1038/s41467-024-47120-y · Cited by 95 · see citing works
Repurposing of Kinase Inhibitors as Broad-Spectrum Antiviral Drugs
Schor, S., & Einav, S. (2017) · DNA and Cell Biology · doi:10.1089/dna.2017.4033 · Cited by 94 · see citing works
Li, X., Li, Z. S., Wu, X., Xiong, Z., Yang, T., Fu, Z., Liu, X., Tan, X., Zhong, F., Wan, X., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00855 · Cited by 93 · see citing works
Jiang, X., Lü, W., Shen, X., Wang, Q., Lv, J., Liu, M., Cheng, F., Zhao, Z., & Pang, X. (2018) · JCI Insight · doi:10.1172/jci.insight.98921 · Cited by 90 · 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
- Authors
- Knight, Z. A., Lin, H., & Shokat, K. M.
- Affiliations
- Rockefeller University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Knight, Zachary A.
- Shokat, Kevan M.
- Venue
- Nature reviews. Cancer
- Published
- 2010-02
- Volume
- 10
- Issue
- 2
- Pages
- 130-137
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC2880454
- OpenAlex
- W2022609682
- Cited by
- 674
- References
- 104
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 21 · 2023: 22 · 2022: 24 · 2021: 29 · 2020: 47 · 2019: 34 · 2018: 45 · 2017: 51 · 2016: 43 · 2015: 48 · 2014: 72 · 2013: 70 · 2012: 43
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5r01eb001987-15)
- National Institute of Diabetes and Digestive and Kidney Diseases (R00DK083531, K99DK083531)
- National Institute of Biomedical Imaging and Bioengineering (R01-EB001987)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- kinase inhibitors, polypharmacology, combination therapy, drug resistance, anticancer drug development
- MeSH terms
- Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Humans, Mutation, Neoplasms, Protein Kinases, Technology, Pharmaceutical, Drug Delivery Systems, Drug Resistance, Neoplasm, RNA, Small Interfering, Protein Kinase Inhibitors, Drug Discovery
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