A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader
Open accessAbstract
Heterobifunctional molecules that recruit E3 ubiquitin ligases, such as cereblon, for targeted protein degradation represent an emerging pharmacological strategy. A major unanswered question is how generally applicable this strategy is to all protein targets. In this study, we designed a multi-kinase degrader by conjugating a highly promiscuous kinase inhibitor with a cereblon-binding ligand, and used quantitative proteomics to discover 28 kinases, including BTK, PTK2, PTK2B, FLT3, AURKA, AURKB, TEC, ULK1, ITK, and nine members of the CDK family, as degradable. This set of kinases is only a fraction of the intracellular targets bound by the degrader, demonstrating that successful degradation requires more than target engagement. The results guided us to develop selective degraders for FLT3 and BTK, with potentials to improve disease treatment. Together, this study demonstrates an efficient approach to triage a gene family of interest to identify readily degradable targets for further studies and pre-clinical developments.
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?
Several mechanisms contribute to increased selectivity of PROTACs, including steric incapability of some targets to form a productive ternary complex, or lack of a suitably positioned lysine residue for ubiquitination.
“Several mechanisms have been shown to contribute to this increase in selectivity. This includes steric incapability of some targets to form a productive ternary complex, or lack of a suitably positioned lysine residue for ubiquitination.62−69”
From Advancing Targeted Protein Degradation via Multiomics Profiling and Artificial Intelligence (2023) · cites this paper as [66]
BTK is one of the most degraded kinases in a promiscuous kinase degrader proteomic analysis, indicating it is a tractable target for degradation.
“Notably, BTK scored as one of the most degraded kinases, indicating that it is a tractable target.”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [14]
DD-03-033 lacks a carbonyl on the glutarimide ring of the thalidomide moiety, a modification that significantly reduces its affinity for CRBN.
“As a negative control, we synthesized DD-03-033 (Figure 1A), an analog of DD-03-007 that lacks a carbonyl on the glutarimide ring of the thalidomide moiety, a modification that significantly reduces its affinity for CRBN.14”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [14]
By converting a multitargeted kinase inhibitor into a degrader, the authors previously profiled the degradable kinome and identified BTK as a tractable target.
“Previously, by converting a multitargeted kinase inhibitor into a degrader, we profiled the degradable kinome and identified BTK as a tractable target.14”
From Bruton tyrosine kinase degradation as a therapeutic strategy for cancer (2019) · cites this paper as [14]
PROTAC selectivity does not necessarily mimic that of its target-binding warhead, but rather depends sensitively on the linker.
“It has further been shown that PROTAC selectivity does not necessarily mimic that of its target-binding warhead, but rather depends sensitively on the linker 20, 23, 24, 33”
From Rationalizing PROTAC-Mediated Ternary Complex Formation Using Rosetta (2021) · cites this paper as [23]
A significant subset of proteins are recalcitrant to targeted protein degradation using current approaches.
“but a significant subset of proteins are recalcitrant to targeted protein degradation using current approaches4,5.”
From Small-molecule-induced polymerization triggers degradation of BCL6 (2020) · cites this paper as [4]
The ability of these PROTACs to degrade mutant forms of BTK was not evaluated.
“However, the ability of these PROTACs to degrade mutant forms of BTK was not evaluated [115].”
From Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies (2020) · cites this paper as [115]
DD-04-015 efficiently and selectively degrades BTK and produces similar antiproliferative activity as RN486 in BTK-dependent TMD8 DLBCL cells.
“The RN486-based degrader, named DD-04-015, efficiently and selectively degraded BTK and produced a similar antiproliferative activity as RN486 in BTK-dependent TMD8 DLBCL cells.”
From Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies (2020) · cites this paper as [115]
TL12-186 degrades multiple kinases including BTK.
“Gray’s group reported the degradation of multiple kinases including BTK by a multi-kinase degrader, TL12-186.”
From Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies (2020) · cites this paper as [115]
A CRBN-recruiting PROTAC based on a promiscuous kinase inhibitor failed to significantly degrade FLT-3, likely due to poor cell permeability.
“In an early study, using a CRBN-recruiting PROTAC based on a promiscuous kinase inhibitor to target multiple kinases failed to significantly degrade FLT-3, likely due to its poor cell permeability [115].”
From Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies (2020) · cites this paper as [115]
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
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,706 · see citing works
limma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv007 · Cited by 40,458 · see citing works
Genome engineering using the CRISPR-Cas9 system
Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013) · Nature Protocols · doi:10.1038/nprot.2013.143 · Cited by 11,133 · see citing works
UniProt: the Universal Protein knowledgebase
Apweiler, R. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh131 · Cited by 7,535 · see citing works
Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis
Edwards, J. C. W., Szczepański, L., Szechiński, J., Filipowicz-Sosnowska, A., Emery, P., Close, D. R., Stevens, R. M., & Shaw, T. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa032534 · Cited by 2,623 · see citing works
Sakamoto, K. M., Kim, K. B., Kumagai, A., Mercurio, F., Crews, C. M., & Deshaies, R. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.141230798 · Cited by 2,609 · 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
B-cell depletion with rituximab in relapsing-remitting multiple sclerosis
Hauser, S. L., Waubant, E., Arnold, D. L., Vollmer, T., Antel, J., Fox, R. J., Bar-Or, A., Panzara, M., Sarkar, N., Agarwal, S., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0706383 · Cited by 2,439 · see citing works
Identification of a Primary Target of Thalidomide Teratogenicity
Ito, T., Ando, H., Suzuki, T., Ogura, T., Hotta, K., Imamura, Y., Yamaguchi, Y., & Handa, H. (2010) · Science · doi:10.1126/science.1177319 · Cited by 2,136 · see citing works
Navarra, S., Guzmán, R., Gallacher, A., Hall, S., Levy, R. A., Jimenez, R., Li, E. K., Thomas, M., Kim, H., Leon, M. G., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(10)61354-2 · Cited by 2,078 · see citing works
Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells
Krönke, J., Udeshi, N. D., Narla, A., Grauman, P., Hurst, S. N., McConkey, M., Svinkina, T., Heckl, D., Comer, E., Li, X., et al. (2014) · Science · doi:10.1126/science.1244851 · Cited by 1,879 · 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
Identifying differentially expressed genes using false discovery rate controlling procedures
Reiner, A., Yekutieli, D., & Benjamini, Y. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btf877 · Cited by 1,765 · see citing works
Phthalimide conjugation as a strategy for in vivo target protein degradation
Winter, G. E., Buckley, D. L., Paulk, J., Roberts, J. M., Souza, A., Dhe-Paganon, S., & Bradner, J. E. (2015) · Science · doi:10.1126/science.aab1433 · Cited by 1,760 · see citing works
Self-citationThe Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins
Lu, G., Middleton, R. E., Sun, H., Naniong, M., Ott, C. J., Mitsiades, C. S., Wong, K.-K., Bradner, J. E., & Kaelin, W. G. (2014) · Science · doi:10.1126/science.1244917 · Cited by 1,583 · see citing works
Self-citationCatalytic in vivo protein knockdown by small-molecule PROTACs
Bondeson, D. P., Mares, A., Smith, I. E. D., Ko, E., Campos, S., Miah, A. H., Mulholland, K. E., Routly, N., Buckley, D. L., Gustafson, J. L., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1858 · Cited by 1,356 · see citing works
Self-citationMcAlister, G. C., Nusinow, D. P., Jedrychowski, M. P., Wühr, M., Huttlin, E. L., Erickson, B. K., Rad, R., Haas, W., & Gygi, S. P. (2014) · Analytical Chemistry · doi:10.1021/ac502040v · Cited by 1,263 · see citing works
Structural basis of PROTAC cooperative recognition for selective protein degradation
Gadd, M. S., Testa, A., Lucas, X., Chan, K.-H., Chen, W., Lamont, D. J., Zengerle, M., & Ciulli, A. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2329 · Cited by 1,242 · see citing works
Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide
Fischer, E. S., Böhm, K., Lydeard, J. R., Yang, H., Stadler, M. B., Cavadini, S., Nagel, J., Serluca, F., Acker, V., Lingaraju, G. M., et al. (2014) · Nature · doi:10.1038/nature13527 · Cited by 1,141 · see citing works
Self-citationHijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4
Lu, J., Qian, Y., Altieri, M., Dong, H., Wang, J., Raina, K., Hines, J., Winkler, J. D., Crew, A. P., Coleman, K., et al. (2015) · Chemistry & Biology · doi:10.1016/j.chembiol.2015.05.009 · Cited by 1,140 · see citing works
Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4
Zengerle, M., Chan, K.-H., & Ciulli, A. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00216 · Cited by 1,056 · see citing works
FDA-approved small-molecule kinase inhibitors
Wu, P., Nielsen, T. E., & Clausen, M. H. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.04.005 · Cited by 1,028 · see citing works
The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis
Carmena, M., Wheelock, M., Funabiki, H., & Earnshaw, W. C. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3474 · Cited by 891 · see citing works
Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS
Krönke, J., Fink, E. C., Hollenbach, P. W., MacBeth, K. J., Hurst, S. N., Udeshi, N. D., Chamberlain, P. P., Mani, D. R., Man, H. W., Gandhi, A. K., et al. (2015) · Nature · doi:10.1038/nature14610 · Cited by 863 · see citing works
PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer
Raina, K., Lu, J., Qian, Y., Altieri, M., Gordon, D., Rossi, A. M. K., Wang, J., Chen, X., Dong, H., Siu, K., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521738113 · Cited by 852 · see citing works
Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15
Han, T., Goralski, M., Gaskill, N., Capota, E., Kim, J., Ting, T. C., Xie, Y., Williams, N. S., & Nijhawan, D. (2017) · Science · doi:10.1126/science.aal3755 · Cited by 762 · see citing works
Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia
Smith, C. C., Wang, Q., Chin, C.-S., Salerno, S. N., Damon, L. E., Levis, M. J., Perl, A. E., Travers, K. J., Wang, S., Hunt, J. P., et al. (2012) · Nature · doi:10.1038/nature11016 · Cited by 738 · see citing works
Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes.
UMEZAWA, H., AOYAGI, T., Hiroyuki, S., HAMADA, M., & TAKEUCHI, T. (1976) · The Journal of Antibiotics · doi:10.7164/antibiotics.29.97 · Cited by 723 · see citing works
A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase
Matyskiela, M. E., Lu, G., Ito, T., Pagarigan, B., Lu, C.-C., Miller, K., Fang, W., Wang, N.-Y., Nguyen, D., Houston, J., et al. (2016) · Nature · doi:10.1038/nature18611 · Cited by 701 · see citing works
Zarrinkar, P. P., Gunawardane, R. N., Cramer, M. D., Gardner, M. F., Brigham, D., Belli, B., Karaman, M. W., Pratz, K. W., Pallares, G., Chao, Q., et al. (2009) · Blood · doi:10.1182/blood-2009-05-222034 · Cited by 641 · see citing works
Schneekloth, A. R., Pucheault, M., Tae, H. S., & Crews, C. M. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.07.114 · Cited by 635 · see citing works
Modular PROTAC design for the degradation of oncogenic BCR-ABL
Lai, A. C., Toure, M., Hellerschmied, D., Salami, J., Jaime‐Figueroa, S., Ko, E., Hines, J., & Crews, C. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201507634 · Cited by 618 · see citing works
Self-citationWeisberg, E., Boulton, C. L., Kelly, L. M., Manley, P. W., Fabbro, D., Meyer, T., Gilliland, D. G., & Griffin, J. D. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00069-7 · Cited by 603 · see citing works
Self-citationBuckley, D. L., Van Molle, I., Gareiss, P. C., Tae, H. S., Michel, J., Noblin, D. J., Jorgensen, W. L., Ciulli, A., & Crews, C. M. (2012) · Journal of the American Chemical Society · doi:10.1021/ja209924v · Cited by 569 · see citing works
Self-citationTargeting Bruton's tyrosine kinase in B cell malignancies
Hendriks, R. W., Yuvaraj, S., & Kil, L. P. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3702 · Cited by 564 · see citing works
Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation
Olson, C. M., Jiang, B., Erb, M. A., Liang, Y., Doctor, Z. M., Zhang, Z., Zhang, T., Kwiatkowski, N., Boukhali, M., Green, J. L., et al. (2018) · Nature Chemical Biology · doi:10.1038/nchembio.2538 · Cited by 552 · see citing works
Self-citationM-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCF <sup>β-TrCP</sup>
Watanabe, N., Arai, H., Nishihara, Y., Taniguchi, M., Watanabe, N., Hunter, T., & Osada, H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307700101 · Cited by 472 · see citing works
A Comprehensive Mathematical Model for Three-Body Binding Equilibria
Douglass, E. F., Miller, C. J., Sparer, G., Shapiro, H., & Spiegel, D. A. (2013) · Journal of the American Chemical Society · doi:10.1021/ja311795d · Cited by 472 · see citing works
Functional Interrogation of the Kinome Using Nucleotide Acyl Phosphates
Patricelli, M. P., Szardenings, A. K., Liyanage, M., Nomanbhoy, T. K., Wu, M., Weissig, H., Aban, A., Chun, D., Tanner, S. W., & Kozarich, J. W. (2006) · Biochemistry · doi:10.1021/bi062142x · Cited by 426 · see citing works
Galdeano, C., Gadd, M. S., Soares, P., Scaffidi, S., Molle, I. V., Birced, I., Hewitt, S. H., Dias, D. M. G., & Ciulli, A. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5011258 · Cited by 424 · see citing works
Bacher, U., Haferlach, C., Kern, W., et al. (2007) · Blood · doi:10.1182/blood-2007-05-091215 · Cited by 412 · see citing works
Itoh, Y., Ishikawa, M., Naito, M., & Hashimoto, Y. (2010) · Journal of the American Chemical Society · doi:10.1021/ja100691p · Cited by 404 · see citing works
Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK
Galkin, A., Melnick, J. S., Kim, S. J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609412103 · Cited by 379 · see citing works
In Situ Kinase Profiling Reveals Functionally Relevant Properties of Native Kinases
Patricelli, M. P., Nomanbhoy, T. K., Wu, J., Brown, H., Zhou, D., Zhang, J., Jagannathan, S., Aban, A., Okerberg, E. S., Herring, C., et al. (2011) · Chemistry & Biology · doi:10.1016/j.chembiol.2011.04.011 · Cited by 357 · see citing works
Self-citationTranscription control by the ENL YEATS domain in acute leukaemia
Erb, M. A., Scott, T. G., Li, B. E., Xie, H., Paulk, J., Seo, H., Souza, A., Roberts, J. M., Dastjerdi, S., Buckley, D. L., et al. (2017) · Nature · doi:10.1038/nature21688 · Cited by 313 · see citing works
Self-citationDegradation of the BAF Complex Factor BRD9 by Heterobifunctional Ligands
Remillard, D., Buckley, D. L., Paulk, J., Brien, G. L., Sonnett, M., Seo, H., Dastjerdi, S., Wühr, M., Dhe‐Paganon, S., Armstrong, S. A., et al. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201611281 · Cited by 294 · see citing works
Self-citationFLT3 mutations in acute myeloid leukemia cell lines
Quentmeier, H., Reinhardt, J., Zaborski, M., & Drexler, H. G. (2003) · Leukemia · doi:10.1038/sj.leu.2402740 · Cited by 285 · see citing works
Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells
Rix, L. L. R., Rix, U., Colinge, J., Hantschel, O. D., Bennett, K. L., Stranzl, T., Müller, A. C., Baumgärtner, C., Valent, P., Augustin, M. A., et al. (2008) · Leukemia · doi:10.1038/leu.2008.334 · Cited by 284 · see citing works
Crenolanib is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants
Galanis, A., Ma, H., Rajkhowa, T., Ramachandran, A., Small, D., Cortes, J. E., & Levis, M. J. (2013) · Blood · doi:10.1182/blood-2013-10-529313 · Cited by 258 · see citing works
FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013?
Levis, M. J. (2013) · Hematology · doi:10.1182/asheducation-2013.1.220 · Cited by 248 · see citing works
Liu, C.-C., Lin, Y., Chen, Y.-H., Chen, C., Pang, L.-Y., Chen, H.-A., Wu, P., Lin, M.-Y., Jiang, S., Tsai, T., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.11.001 · Cited by 224 · see citing works
Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity
Boschelli, D. H., Ye, F., Wang, Y. D., Dutia, M. D., Johnson, S. L., Wu, B., Miller, K., Powell, D. W., Yaczko, D., Young, M., et al. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm0102250 · Cited by 218 · 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
Crenolanib is active against models of drug-resistant FLT3-ITD−positive acute myeloid leukemia
Zimmerman, E. I., Turner, D. C., Buaboonnam, J., Hu, S., Orwick, S. J., Roberts, M. S., Janke, L. J., Ramachandran, A., Stewart, C. F., Inaba, H., et al. (2013) · Blood · doi:10.1182/blood-2013-07-513044 · Cited by 180 · see citing works
Small Molecules Destabilize cIAP1 by Activating Auto-ubiquitylation
Sekine, K., Takubo, K., Kikuchi, R., Nishimoto, M., Kitagawa, M., Abe, F., Nishikawa, K., Tsuruo, T., & Naito, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709525200 · Cited by 173 · see citing works
Crystal Structures of Anaplastic Lymphoma Kinase in Complex with ATP Competitive Inhibitors
Bossi, R. T., Saccardo, M. B., Ardini, E., Menichincheri, M., Rusconi, L., Magnaghi, P., Orsini, P., Avanzi, N. R., Borgia, A. L., Nesi, M., et al. (2010) · Biochemistry · doi:10.1021/bi1005514 · Cited by 171 · see citing works
The evolving role of FLT3 inhibitors in acute myeloid leukemia: quizartinib and beyond
Wander, S. A., Levis, M. J., & Fathi, A. T. (2014) · Therapeutic Advances in Hematology · doi:10.1177/2040620714532123 · Cited by 166 · see citing works
Deshaies, R. J. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1887 · Cited by 162 · see citing works
Örning, L., Krivi, G. G., & Fitzpatrick, F. A. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)52303-6 · Cited by 158 · see citing works
Nguyen, H. G., Chinnappan, D., Urano, T., & Ravid, K. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.12.4977-4992.2005 · Cited by 156 · see citing works
Proteasome inhibitors induce FLT3-ITD degradation through autophagy in AML cells
Larrue, C., Saland, E., Boutzen, H., Vergez, F., David, M., Joffre, C., Tamburini, J., Delabesse, É., Manenti, S., Sarry, J., et al. (2015) · Blood · doi:10.1182/blood-2015-05-646497 · Cited by 135 · see citing works
Degradation of human Aurora‐A protein kinase is mediated by hCdh1
Taguchi, S.-I., Honda, K., Sugiura, K., Yamaguchi, A., Furukawa, K., & Urano, T. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02711-4 · Cited by 113 · see citing works
Lou, Y. C., Han, X., Kuglstatter, A., Kondru, R. K., Sweeney, Z. K., Soth, M., McIntosh, J. E., Litman, R., Suh, J. M., Koçer, B., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500305p · Cited by 112 · see citing works
Weisberg, E., Ray, A., Nelson, E. A., Adamia, S., Barrett, R., Sattler, M., Zhang, C., Daley, J. F., Frank, D. A., Fox, E., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025351 · Cited by 49 · see citing works
Self-citationNomanbhoy, T. K., Sharma, G., Brown, H., Wu, J., Aban, A., Vogeti, S., Alemayehu, S., Sykes, M., Rosenblum, J. S., & Kozarich, J. W. (2016) · Biochemistry · doi:10.1021/acs.biochem.6b00629 · Cited by 31 · see citing works
Sorscher, S. M. (2010) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2010.0110 · Cited by 23 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
PROTAC targeted protein degraders: the past is prologue
Békés, M., Langley, D. R., & Crews, C. M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00371-6 · Cited by 3,395 · see citing works
Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery
Burslem, G. M., & Crews, C. M. (2020) · Cell · doi:10.1016/j.cell.2019.11.031 · Cited by 1,079 · see citing works
Kinase inhibitors: the road ahead
Ferguson, F. M., & Gray, N. S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.21 · Cited by 1,009 · see citing works
Self-citationTargeted protein degradation: expanding the toolbox
Schapira, M., Calabrese, M. F., Bullock, A. N., & Crews, C. M. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0047-y · Cited by 960 · see citing works
A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity
Khan, S., Zhang, X., Lv, D., Zhang, Q., He, Y., Zhang, P., Liu, X., Thummuri, D., Yuan, Y., Wiegand, J. S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0668-z · Cited by 688 · see citing works
Plasticity in binding confers selectivity in ligand-induced protein degradation
Nowak, R. P., DeAngelo, S. L., Buckley, D., He, Z., Donovan, K. A., An, J., Safaee, N., Jedrychowski, M. P., Ponthier, C. M., Ishoey, M., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0055-y · Cited by 615 · see citing works
Self-citationDifferential PROTAC substrate specificity dictated by orientation of recruited E3 ligase
Smith, B. E., Wang, S. L., Jaime-Figueroa, S., Harbin, A., Wang, J., Hamman, B. D., & Crews, C. M. (2019) · Nature Communications · doi:10.1038/s41467-018-08027-7 · Cited by 517 · see citing works
Electrophilic PROTACs that degrade nuclear proteins by engaging DCAF16
Zhang, X., Crowley, V. M., Wucherpfennig, T. G., Dix, M. M., & Cravatt, B. F. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0279-5 · Cited by 487 · see citing works
Development of targeted protein degradation therapeutics
Chamberlain, P. P., & Hamann, L. G. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0362-y · Cited by 489 · see citing works
Delineating the role of cooperativity in the design of potent PROTACs for BTK
Zorba, A., Nguyen, C., Xu, Y., Starr, J., Borzilleri, K., Smith, J., Zhu, H., Farley, K. A., Ding, W., Schiemer, J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1803662115 · Cited by 419 · see citing works
Edmondson, S. D., Yang, B., & Fallan, C. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.04.030 · Cited by 422 · see citing works
Current strategies for the design of PROTAC linkers: a critical review
Troup, R. I., Fallan, C., & Baud, M. G. J. (2020) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2020.00018 · Cited by 424 · see citing works
Buhimschi, A. D., Armstrong, H. A., Toure, M., Jaime-Figueroa, S., Chen, T. L., Lehman, A. M., Woyach, J. A., Johnson, A. J., Byrd, J. C., & Crews, C. M. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00391 · Cited by 394 · see citing works
Light-Induced Protein Degradation with Photocaged PROTACs
Xue, G., Wang, K., Zhou, D., Zhong, H., & Pan, Z. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b06422 · Cited by 377 · see citing works
An, S., & Fu, L. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.09.005 · Cited by 363 · 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
Self-citationHines, J., Lartigue, S., Dong, H., Qian, Y., & Crews, C. M. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2918 · Cited by 348 · see citing works
Degradation of proteins by PROTACs and other strategies
Wang, Y., Jiang, X., Feng, F., Liu, W., & Sun, H. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.08.001 · Cited by 335 · see citing works
Zoppi, V., Hughes, S. J., Maniaci, C., Testa, A., Gmaschitz, T., Wieshofer, C., Koegl, M., Riching, K. M., Daniels, D. L., Spallarossa, A., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01413 · Cited by 336 · see citing works
Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules
Nabet, B., Ferguson, F. M., Seong, B. K. A., Kuljanin, M., Leggett, A. L., Mohardt, M. L., Robichaud, A., Conway, A. S., Buckley, D. L., Mancias, J. D., et al. (2020) · doi:10.1101/2020.03.13.980946 · Cited by 312 · see citing works
Self-citationAddressing Kinase-Independent Functions of Fak via PROTAC-Mediated Degradation
Cromm, P. M., Samarasinghe, K. T. G., Hines, J., & Crews, C. M. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b08008 · Cited by 293 · see citing works
Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models
Silva, M. C., Ferguson, F. M., Cai, Q., Donovan, K. A., Nandi, G., Patnaik, D., Zhang, T., Huang, H.-T., Lucente, D. E., Dickerson, B. C., et al. (2019) · eLife · doi:10.7554/elife.45457 · Cited by 283 · see citing works
Self-citationSmall-molecule-induced polymerization triggers degradation of BCL6
Słabicki, M., Yoon, H., Koeppel, J., Nitsch, L., Roy Burman, S. S., Di Genua, C., Donovan, K. A., Sperling, A. S., Hunkeler, M., Tsai, J. M., et al. (2020) · Nature · doi:10.1038/s41586-020-2925-1 · Cited by 270 · see citing works
Self-citationPROTACs: great opportunities for academia and industry (an update from 2020 to 2021)
He, M., Cao, C., Ni, Z., Liu, Y., Song, P., Hao, S., He, Y., Sun, X., & Rao, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00999-9 · Cited by 283 · see citing works
Development of dual and selective degraders of cyclin-dependent kinases 4 and 6
Jiang, B., Wang, E. S., Donovan, K. A., Liang, Y., Fischer, E. S., Zhang, T., & Gray, N. S. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201901336 · Cited by 272 · see citing works
Self-citationHomolog-Selective Degradation as a Strategy to Probe the Function of CDK6 in AML
Brand, M., Jiang, B., Bauer, S., Donovan, K. A., Liang, Y., Wang, E. S., Nowak, R. P., Yuan, J. C., Zhang, T., Kwiatkowski, N., et al. (2019) · Cell Chemical Biology · doi:10.1016/j.chembiol.2018.11.006 · Cited by 258 · see citing works
Self-citationde Wispelaere, M., Du, G., Donovan, K. A., Zhang, T., Eleuteri, N. A., Yuan, J. C., Kalabathula, J., Nowak, R. P., Fischer, E. S., Gray, N. S., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11429-w · Cited by 237 · see citing works
Self-citationProteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK)
Zhang, C., Han, X.-R., Yang, X., Jiang, B., Liu, J., Xiong, Y., & Jin, J. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.03.071 · Cited by 226 · see citing works
Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation
Burslem, G. M., Schultz, A. R., Bondeson, D. P., Eide, C. A., Savage Stevens, S. L., Druker, B. J., & Crews, C. M. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-1236 · Cited by 212 · see citing works
PRosettaC: Rosetta Based Modeling of PROTAC Mediated Ternary Complexes
Zaidman, D., Prilusky, J., & London, N. (2020) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c00589 · Cited by 224 · see citing works
Proteolysis‐targeting chimeras in drug development: A safety perspective
Moreau, K., Coen, M., Zhang, A. X., Pachl, F., Castaldi, M. P., Dahl, G., Boyd, H., Scott, C., & Newham, P. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15014 · Cited by 229 · see citing works
Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands
Gechijian, L. N., Buckley, D. L., Lawlor, M. A., Reyes, J. M., Paulk, J., Ott, C. J., Winter, G. E., Erb, M. A., Scott, T. G., Xu, M., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0010-y · Cited by 222 · see citing works
Self-citationEfficient targeted degradation via reversible and irreversible covalent PROTACs
Gabizon, R., Shraga, A., Gehrtz, P., Livnah, E., Gurwicz, N., Avram, L., Unger, T., Albeck, S., Shulman, Z., & London, N. (2020) · doi:10.26434/chemrxiv.11494398.v1 · Cited by 213 · see citing works
Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK)
Powell, C. E., Gao, Y., Tan, L., Donovan, K. A., Nowak, R. P., Loehr, A., Bahcall, M., Fischer, E. S., Jänne, P. A., George, R. E., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01655 · Cited by 198 · see citing works
Self-citationPROTAC-Mediated Degradation of Bruton’s Tyrosine Kinase Is Inhibited by Covalent Binding
Tinworth, C. P., Lithgow, H., Dittus, L., Bassi, Z. I., Hughes, S. E., Muelbaier, M., Dai, H., Smith, I. E. D., Kerr, W. J., Burley, G. A., et al. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.8b01094 · Cited by 195 · see citing works
PROTACs: A novel strategy for cancer therapy
Liu, J., Ma, J., Liu, Y., Xia, J., Li, Y., Wang, Z. P., & Wei, W. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.02.006 · Cited by 186 · see citing works
Self-citationLuo, M., Spradlin, J. N., Boike, L., Tong, B., Brittain, S. M., McKenna, J. M., Tallarico, J. A., Schirle, M., Maimone, T. J., & Nomura, D. K. (2021) · Cell Chemical Biology · doi:10.1016/j.chembiol.2021.01.005 · Cited by 186 · see citing works
Harnessing the Power of Proteolysis for Targeted Protein Inactivation
Verma, R., Mohl, D., & Deshaies, R. J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.01.010 · Cited by 185 · see citing works
Burslem, G. M., Song, J., Chen, X., Hines, J., & Crews, C. M. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b10320 · Cited by 176 · see citing works
Lim, S., Khoo, R., Peh, K. M., Teo, J., Chang, S. C., Ng, S., Beilhartz, G. L., Melnyk, R. A., Johannes, C. W., Brown, C. J., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1920251117 · Cited by 170 · see citing works
Ishoey, M., Chorn, S., Singh, N., Jaeger, M. G., Brand, M., Paulk, J., Bauer, S., Erb, M. A., Parapatics, K., Müller, A. C., et al. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.7b00969 · Cited by 177 · see citing works
Self-citationBruton tyrosine kinase degradation as a therapeutic strategy for cancer
Dobrovolsky, D., Wang, E. S., Morrow, S., Leahy, C., Faust, T., Nowak, R. P., Donovan, K. A., Yang, G., Li, Z., Fischer, E. S., et al. (2019) · Blood · doi:10.1182/blood-2018-07-862953 · Cited by 169 · see citing works
Self-citationDrummond, M. L., Henry, A., Li, H., & Williams, C. I. (2020) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.0c00897 · Cited by 166 · 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
Discovery and resistance mechanism of a selective CDK12 degrader
Jiang, B., Gao, Y., Che, J., Lu, W., Kaltheuner, I. H., Dries, R., Kalocsay, M., Berberich, M. J., Jiang, J., You, I., et al. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00765-y · Cited by 150 · see citing works
Self-citationDT2216—a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas
He, Y., Koch, R., Budamagunta, V., Zhang, P., Zhang, X., Khan, S., Thummuri, D., Ortiz, Y. T., Zhang, X., Lv, D., et al. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00928-9 · Cited by 139 · see citing works
Popow, J., Arnhof, H., Bader, G., Berger, H., Ciulli, A., Covini, D., Dank, C., Gmaschitz, T., Greb, P., Karolyi-Özguer, J., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01826 · Cited by 138 · see citing works
Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide
Jan, M., Sperling, A. S., & Ebert, B. L. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00479-z · Cited by 137 · see citing works
Zhao, Q., Ren, C., Liu, L., Chen, J., Shao, Y., Sun, N., Sun, R., Kong, Y., Ding, X., Zhang, X., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01264 · Cited by 134 · see citing works
Targeted protein degradation and the enzymology of degraders
Fisher, S. L., & Phillips, A. J. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.05.004 · Cited by 126 · see citing works
Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies
He, Y., Khan, S., Huo, Z., Lv, D., Zhang, X., Liu, X., Yuan, Y., Hromas, R., Xu, M., Zheng, G., et al. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00924-z · Cited by 126 · see citing works
Wang, Z., He, N., Guo, Z., Niu, C., Song, T., Guo, Y., Cao, K., Wang, A., Zhu, J., Zhang, X., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00919 · Cited by 120 · see citing works
A Nimbolide-Based Kinase Degrader Preferentially Degrades Oncogenic BCR-ABL
Tong, B., Spradlin, J. N., Novaes, L. F. T., Zhang, E., Hu, X., Moeller, M., Brittain, S. M., McGregor, L. M., McKenna, J. M., Tallarico, J. A., et al. (2020) · ACS Chemical Biology · doi:10.1021/acschembio.0c00348 · Cited by 118 · see citing works
Snapshots and ensembles of BTK and cIAP1 protein degrader ternary complexes
Schiemer, J., Horst, R., Meng, Y., Montgomery, J. I., Xu, Y., Feng, X., Borzilleri, K., Uccello, D. P., Leverett, C., Brown, S., et al. (2021) · Nature Chemical Biology · doi:10.1038/s41589-020-00686-2 · Cited by 113 · see citing works
Cereblon modulators: Low molecular weight inducers of protein degradation
Chamberlain, P. P., & Cathers, B. E. (2019) · Drug Discovery Today: Technologies · doi:10.1016/j.ddtec.2019.02.004 · Cited by 106 · see citing works
From Inhibition to Degradation: Targeting the Antiapoptotic Protein Myeloid Cell Leukemia 1 (MCL1)
Papatzimas, J. W., Gorobets, E., Maity, R., Muniyat, M. I., MacCallum, J. L., Neri, P., Bahlis, N. J., & Derksen, D. J. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00455 · Cited by 103 · see citing works
PROTAC degraders as chemical probes for studying target biology and target validation
Němec, V., Schwalm, M. P., Müller, S., & Knapp, S. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00478j · Cited by 98 · see citing works
Foley, C. A., Potjewyd, F., Lamb, K. N., James, L. I., & Frye, S. V. (2020) · ACS Chemical Biology · doi:10.1021/acschembio.9b00972 · Cited by 89 · see citing works
Jaime-Figueroa, S., Buhimschi, A. D., Toure, M., Hines, J., & Crews, C. M. (2020) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.126877 · Cited by 88 · see citing works
Bai, N., Riching, K. M., Makaju, A., Wu, H., Acker, T. M., Ou, S.-C., Zhang, Y., Shen, X., Bulloch, D. N., Rui, H., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101653 · Cited by 77 · see citing works
Development of PDE6D and CK1α Degraders through Chemical Derivatization of FPFT-2216
Teng, M., Lu, W., Donovan, K. A., Sun, J., Krupnick, N. M., Nowak, R. P., Li, Y.-D., Sperling, A. S., Zhang, T., Ebert, B. L., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01832 · Cited by 63 · see citing works
Self-citationTargeting of the FOXM1 Oncoprotein by E3 Ligase-Assisted Degradation
Luo, G., Lin, X., Vega-Medina, A., Xiao, M., Li, G., Wei, H., Velázquez-Martínez, C. A., & Xiang, H. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01069 · Cited by 56 · see citing works
A critical evaluation of the approaches to targeted protein degradation for drug discovery
Chopra, R., Sadok, A., & Collins, I. (2019) · Drug Discovery Today: Technologies · doi:10.1016/j.ddtec.2019.02.002 · Cited by 53 · see citing works
Advancing Targeted Protein Degradation via Multiomics Profiling and Artificial Intelligence
Duran-Frigola, M., Cigler, M., & Winter, G. E. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.2c11098 · Cited by 50 · see citing works
Targeting oncoproteins with a positive selection assay for protein degraders
Koduri, V., Duplaquet, L., Lampson, B. L., Wang, A. C., Sabet, A. H., Ishoey, M., Paulk, J., Teng, M., Harris, I. S., Endress, J. E., et al. (2021) · Science Advances · doi:10.1126/sciadv.abd6263 · Cited by 44 · see citing works
Self-citationIdentification and characterization of cancer vulnerabilities via targeted protein degradation
Mayor-Ruiz, C., & Winter, G. E. (2019) · Drug Discovery Today: Technologies · doi:10.1016/j.ddtec.2018.12.003 · Cited by 33 · see citing works
Unifying Catalysis Framework to Dissect Proteasomal Degradation Paradigms
Rodriguez-Rivera, F. P., & Levi, S. M. (2021) · ACS Central Science · doi:10.1021/acscentsci.1c00389 · Cited by 30 · see citing works
Dixon, T., MacPherson, D., Mostofian, B., Dauzhenka, T., Lotz, S., McGee, D., Shechter, S., Shrestha, U. R., Wiewiora, R., McDargh, Z. A., et al. (2021) · doi:10.1101/2021.09.26.461830 · Cited by 7 · see citing works
Self-citation
- Authors
- Huang, H.-T., Dobrovolsky, D., Paulk, J., Yang, G., Weisberg, E. L., Doctor, Z. M., Buckley, D. L., Cho, J.-H., Ko, E., Jang, J., Shi, K., Choi, H. G., Griffin, J. D., Li, Y., Treon, S. P., Fischer, E. S., Bradner, J. E., Tan, L., & Gray, N. S.
- Affiliations
- Harvard University (US)
- Dana-Farber Cancer Institute (US)
- Daegu-Gyeongbuk Medical Innovation Foundation (KR)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Tan, Li
- Gray, Nathanael S.
- ORCID
- Venue
- Cell Chemical Biology
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 25
- Issue
- 1
- Pages
- 88-99.e6
- ISSN
- 2451-9448 (ISSN-L)
- 2451-9456
- PMC
- PMC6427047
- OpenAlex
- W2767426216
- Cited by
- 437
- References
- 66
- Citations by year
- 2026: 28 · 2025: 45 · 2024: 52 · 2023: 46 · 2022: 64 · 2021: 55 · 2020: 65 · 2019: 53 · 2018: 27
- FWCI
- 16.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell chemical biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA214608)
- Damon Runyon Cancer Research Foundation (DRG-2196-14)
- Roche
- Harvard Medical School
- Dana-Farber Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- cereblon, heterobifunctional molecules, targeted protein degradation, E3 ubiquitin ligase, kinome, Bruton's tyrosine kinase, FLT3, cyclin-dependent kinases, AURKA, Aurora B kinase, target identification, chemoproteomics, quantitative proteomics
- MeSH terms
- Agammaglobulinaemia Tyrosine Kinase, Humans, Proteomics, Protein Kinase Inhibitors, fms-Like Tyrosine Kinase 3, Proteolysis
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
