Cited by 346Protein Degradation and InhibitorsChemical Synthesis and AnalysisComputational Drug Discovery Methods

The DOI matches its Crossref record; 124 of the 124 references it cites were found in a registry or an index.

WD40 repeat domain proteins: a novel target class?

Open access

Schapira, Matthieu, Tyers, Mike, Torrent, Maricel, Arrowsmith, Cheryl H.·2017·Nature Reviews Drug Discovery

DOI 10.1038/nrd.2017.179PMC PMC5975957

Open this paper in CoChat — free account

Abstract

Antagonism of protein-protein interactions (PPIs) with small molecules is becoming more feasible as a therapeutic approach. Successful PPI inhibitors tend to target proteins containing deep peptide-binding grooves or pockets rather than the more common large, flat protein interaction surfaces. Here, we review one of the most abundant PPI domains in the human proteome, the WD40 repeat (WDR) domain, which has a central peptide-binding pocket and is a member of the β-propeller domain-containing protein family. Recently, two WDR domain-containing proteins, WDR5 and EED, as well as other β-propeller domains have been successfully targeted by potent, specific, cell-active, drug-like chemical probes. Could WDR domains be a novel target class for drug discovery? Although the research is at an early stage and therefore not clinically validated, cautious optimism is justified, as WDR domain-containing proteins are involved in multiple disease-associated pathways. The druggability and structural diversity of WDR domain binding pockets suggest that understanding how to target this prevalent domain class will open up areas of disease biology that have so far resisted drug discovery efforts.

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

Crossref · 10.1038/nrd.2017.179

Cites

124 of 124 references verified0 citation errors · 0 not checkable

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Epigenetic Regulations of GABAergic Neurotransmission: Relevance for Neurological Disorders and Epigenetic Therapy
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,951
Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670
The Reactome pathway Knowledgebase
Fabregat, A., Sidiropoulos, K., Garapati, P., Gillespie, M., Hausmann, K., Haw, R., Jassal, B., Jupe, S., Korninger, F., McKay, S., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1351 · Cited by 5,605
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T. (2005) · Nature · doi:10.1038/nature03443 · Cited by 5,198
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661
Selective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262
BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc
Delmore, J. E., Issa, G. C., Lemieux, M. E., Rahl, P. B., Shi, J., Jacobs, H. M., Kastritis, E., Gilpatrick, T., Paranal, R. M., Qi, J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.017 · Cited by 2,888
Protacs: Chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation
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
The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability
Niesen, F., Berglund, H., & Vedadi, M. (2007) · Nature Protocols · doi:10.1038/nprot.2007.321 · Cited by 2,420
Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia
Roberts, A. W., Davids, M. S., Pagel, J. M., Kahl, B. S., Puvvada, S. D., Gerecitano, J. F., Kipps, T. J., Anderson, M. A., Brown, J. R., Gressick, L. A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1513257 · Cited by 1,930
The Reactome pathway knowledgebase
Croft, D., Mundo, A. F., Haw, R., Milacic, M., Weiser, J., Wu, G., Caudy, M., Garapati, P., Gillespie, M., Kamdar, M. R., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1102 · Cited by 1,889
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
EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations
McCabe, M. T., Ott, H. M., Ganji, G., Korenchuk, S., Thompson, C., Van Aller, G. S., Liu, Y., Graves, A. P., III, A. D. P., Diaz, E., et al. (2012) · Nature · doi:10.1038/nature11606 · Cited by 1,786
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
Mechanism of auxin perception by the TIR1 ubiquitin ligase
Tan, X., Calderon-Villalobos, L. I. A., Sharon, M., Zheng, C., Robinson, C. V., Estelle, M., & Zheng, N. (2007) · Nature · doi:10.1038/nature05731 · Cited by 1,688
The 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
Jasmonate perception by inositol-phosphate-potentiated COI1–JAZ co-receptor
Sheard, L. B., Tan, X., Mao, H., Withers, J., Ben-Nissan, G., Hinds, T. R., Kobayashi, Y., Hsu, F.-F., Sharon, M., Browse, J., et al. (2010) · Nature · doi:10.1038/nature09430 · Cited by 1,497
Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study
Healy, D. G., Falchi, M., O'Sullivan, S. S., Bonifati, V., Durr, A., Bressman, S., Brice, A., Aasly, J., Zabetian, C. P., Goldwurm, S., et al. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70117-0 · Cited by 1,425
Epigenetic protein families: a new frontier for drug discovery
Arrowsmith, C. H., Bountra, C., Fish, P. V., Lee, K., & Schapira, M. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3674 · Cited by 1,327
Self-citation
The anaphase promoting complex/cyclosome: a machine designed to destroy
Peters, J.-M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1988 · Cited by 1,315
Role of the polycomb protein EED in the propagation of repressive histone marks
Margueron, R., Justin, N., Ohno, K., Sharpe, M. L., Son, J., Drury, W. J., Voigt, P., Martin, S. R., Taylor, W. R., Marco, V. D., et al. (2009) · Nature · doi:10.1038/nature08398 · Cited by 1,281
Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity
West, A. B., Moore, D. J., Biskup, S., Bugayenko, A., Smith, W. W., Ross, C. A., Dawson, V. L., & Dawson, T. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507360102 · Cited by 1,228
Small molecules, big targets: drug discovery faces the protein–protein interaction challenge
Scott, D. E., Bayly, A. R., Abell, C., & Skidmore, J. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.29 · Cited by 1,137
Isolation of a Miller–Dicker lissencephaly gene containing G protein β-subunit-like repeats
Reiner, O., Carrozzo, R., Shen, Y. H., Wehnert, M., Faustinella, F., Dobyns, W. B., Caskey, C. T., & Ledbetter, D. H. (1993) · Nature · doi:10.1038/364717a0 · Cited by 1,057
PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene
Rahman, N., Seal, S., Thompson, D. J., Kelly, P. F., Renwick, A., Elliott, A., Reid, S., Spanova, K., Barfoot, R., Chagtai, T., et al. (2006) · Nature Genetics · doi:10.1038/ng1959 · Cited by 1,026
The Mechanisms behind the Therapeutic Activity of BET Bromodomain Inhibition
Shi, J., & Vakoc, C. R. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.016 · Cited by 888
Control of BRCA2 Cellular and Clinical Functions by a Nuclear Partner, PALB2
Xia, B., Sheng, Q., Nakanishi, K., Ohashi, A., Wu, J., Christ, N., Liu, X., Jasin, M., Couch, F. J., & Livingston, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.05.022 · Cited by 861
A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells
Knutson, S. K., Wigle, T. J., Warholic, N. M., Sneeringer, C. J., Allain, C. J., Klaus, C. R., Sacks, J. D., Raimondi, A., Majer, C. R., Song, J., et al. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1084 · Cited by 776
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
Association of a human G-protein β3 subunit variant with hypertension
Siffert, W., Rosskopf, D., Siffert, G., Busch, S., Moritz, A., Erbel, R., Sharma, A. M., Ritz, E., Wichmann, H. ‐., Jakobs, K. H., et al. (1998) · Nature Genetics · doi:10.1038/ng0198-45 · Cited by 726
MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells
Kryukov, G. V., Wilson, F. H., Ruth, J. R., Paulk, J., Tsherniak, A., Marlow, S. E., Vazquez, F., Weir, B. A., Fitzgerald, M. E., Tanaka, M., et al. (2016) · Science · doi:10.1126/science.aad5214 · Cited by 688
Design, synthesis and selection of DNA-encoded small-molecule libraries
Clark, M., Acharya, R. A., Arico-Muendel, C. C., Belyanskaya, S. L., Benjamin, D. R., Carlson, N. R., Chiu, C. H., Creaser, S. P., Cuozzo, J. W., Davie, C. P., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.211 · Cited by 682
Molecular architecture and assembly of the DDB1–CUL4A ubiquitin ligase machinery
Angers, S., Li, T., Yi, X., MacCoss, M. J., Moon, R. T., & Zheng, N. (2006) · Nature · doi:10.1038/nature05175 · Cited by 674
WD40 proteins propel cellular networks
Stirnimann, C. U., Petsalaki, E., Russell, R. B., & Müller, C. W. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.04.003 · Cited by 655
Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer
Reid, S., Schindler, D., Hanenberg, H., Barker, K., Hanks, S., Kalb, R., Neveling, K., Kelly, P., Seal, S., Freund, M., et al. (2007) · Nature Genetics · doi:10.1038/ng1947 · Cited by 642
Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction to Reactivate p53 Function: A Novel Approach for Cancer Therapy
Shangary, S., & Wang, S. (2009) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094723 · Cited by 623
Kinase activity of mutant LRRK2 mediates neuronal toxicity
Smith, W. W., Pei, Z., Jiang, H., Dawson, V. L., Dawson, T. M., & Ross, C. A. (2006) · Nature Neuroscience · doi:10.1038/nn1776 · Cited by 619
Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5
Mavrakis, K. J., McDonald, E. R., Schlabach, M. R., Billy, E., Hoffman, G. R., deWeck, A., Ruddy, D. A., Venkatesan, K., Yu, J., McAllister, G., et al. (2016) · Science · doi:10.1126/science.aad5944 · Cited by 607
A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models
Chan-Penebre, E., Kuplast, K. G., Majer, C. R., Boriack-Sjodin, P. A., Wigle, T. J., Johnston, L. D., Rioux, N., Munchhof, M. J., Jin, L., Jacques, S. L., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1810 · Cited by 569
Role of the Clathrin Terminal Domain in Regulating Coated Pit Dynamics Revealed by Small Molecule Inhibition
von Kleist, L., Stahlschmidt, W., Bulut, H., Gromova, K. V., Puchkov, D., Robertson, M. J., MacGregor, K. A., Tomilin, N. V., Pechstein, A., Chau, N., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.025 · Cited by 569
Structural Basis for Phosphodependent Substrate Selection and Orientation by the SCFCdc4 Ubiquitin Ligase
Orlicky, S. M., Tang, X., Willems, A. R., Tyers, M., & Sicheri, F. (2003) · Cell · doi:10.1016/s0092-8674(03)00034-5 · Cited by 515
Self-citation
Prolyl Oligopeptidase
Fülöp, V., Böcskei, Z., & Polgár, L. (1998) · Cell · doi:10.1016/s0092-8674(00)81416-6 · Cited by 500
Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth
Zhu, J., Sammons, M. A., Donahue, G., Dou, Z., Vedadi, M., Getlik, M., Barsyte-Lovejoy, D., Al-awar, R., Katona, B. W., Shilatifard, A., et al. (2015) · Nature · doi:10.1038/nature15251 · Cited by 493
Self-citation
A recurrent mutation in PALB2 in Finnish cancer families
Erkko, H., Xia, B., Nikkilä, J., Schleutker, J., Syrjäkoski, K., Mannermaa, A., Kallioniemi, A. H., Pylkäs, K., Karppinen, S., Rapakko, K., et al. (2007) · Nature · doi:10.1038/nature05609 · Cited by 471
Structure of a Fbw7-Skp1-Cyclin E Complex: Multisite-Phosphorylated Substrate Recognition by SCF Ubiquitin Ligases
Hao, B., Oehlmann, S., Sowa, M. E., Harper, J. W., & Pavletich, N. P. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.02.022 · Cited by 469
Fanconi anemia is associated with a defect in the BRCA2 partner PALB2
Xia, B., Dorsman, J. C., Ameziane, N., de Vries, Y., Rooimans, M. A., Sheng, Q., Pals, G., Errami, A., Gluckman, E., Llera, J., et al. (2007) · Nature Genetics · doi:10.1038/ng1942 · Cited by 465
An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1
Konze, K. D., Ma, A., Li, F., Baršytė-Lovejoy, D., Parton, T., MacNevin, C. J., Liu, F., Gao, C., Huang, X., Kuznetsova, E., et al. (2013) · ACS Chemical Biology · doi:10.1021/cb400133j · Cited by 463
Self-citation
Lis1 and doublecortin function with dynein to mediate coupling of the nucleus to the centrosome in neuronal migration
Tanaka, T., Serneo, F. F., Higgins, C., Gambello, M. J., Wynshaw-Boris, A. J., & Gleeson, J. G. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200309025 · Cited by 436
Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2
Deng, X., Dzamko, N. L., Prescott, A. R., Davies, P., Liu, Q., Yang, Q., Lee, J., Patricelli, M. P., Nomanbhoy, T. K., Alessi, D. R., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.538 · Cited by 434
Target validation using chemical probes
Bunnage, M. E., Chekler, E. L. P., & Jones, L. H. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1197 · Cited by 424
SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2
Kim, K. H., Kim, W., Howard, T. P., Vázquez, F., Tsherniak, A., Wu, J. N., Wang, W., Haswell, J. R., Walensky, L. D., Hahn, W. C., et al. (2015) · Nature Medicine · doi:10.1038/nm.3968 · Cited by 415
Selective degradation of splicing factor CAPERα by anticancer sulfonamides
Uehara, T., Minoshima, Y., Sagane, K., Sugi, N. H., Mitsuhashi, K. O., Yamamoto, N., Kamiyama, H., Takahashi, K., Kotake, Y., Uesugi, M., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2363 · Cited by 396
The RACK1 Scaffold Protein: A Dynamic Cog in Cell Response Mechanisms
McCahill, A., Warwicker, J., Bolger, G. B., Houslay, M. D., & Yarwood, S. J. (2002) · Molecular Pharmacology · doi:10.1124/mol.62.6.1261 · Cited by 386
Fluorescence polarization assays in small molecule screening
Lea, W., & Simeonov, A. M. (2010) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2011.537322 · Cited by 382
The art of the chemical probe
Frye, S. V. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.296 · Cited by 381
The cancer epigenome: Concepts, challenges, and therapeutic opportunities
Dawson, M. A. (2017) · Science · doi:10.1126/science.aam7304 · Cited by 377
Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance
Migliori, V., Müller, J., Phalke, S., Low, D. H. P., Bezzi, M., Mok, W. C., Sahu, S. K., Gunaratne, J., Capasso, P., Bassi, C., et al. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2209 · Cited by 360
Targeted disruption of the EZH2–EED complex inhibits EZH2-dependent cancer
Kim, W., Bird, G. H., Neff, T., Guo, G., Kerenyi, M. A., Walensky, L. D., & Orkin, S. H. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1331 · Cited by 351
Tumor suppression by the Fbw7 ubiquitin ligase: mechanisms and opportunities
Davis, R. J., Welcker, M., & Clurman, B. E. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.09.013 · Cited by 343
Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease
Lee, B. D., Shin, J.-H., VanKampen, J., Petrucelli, L., West, A. B., Ko, H. S., Lee, Y.-I., Maguire-Zeiss, K. A., Bowers, W. J., Federoff, H. J., et al. (2010) · Nature Medicine · doi:10.1038/nm.2199 · Cited by 329
Monoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein–Protein Interaction with High Cell Potency Identified by Fragment-Based Discovery
Davies, T. G., Wixted, W. E., Coyle, J. E., Griffiths-Jones, C., Hearn, K., McMenamin, R., Norton, D., Rich, S. J., Richardson, C., Saxty, G., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00228 · Cited by 322
An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED
Qi, W., Zhao, K., Gu, J., Huang, Y., Wang, Y., Zhang, H., Zhang, M., Zhang, J., Yu, Z., Li, L., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2304 · Cited by 316
A multi-crystal method for extracting obscured crystallographic states from conventionally uninterpretable electron density
Pearce, N. M., Krojer, T. J., Bradley, A. R., Collins, P. M., Nowak, R. P., Talon, R., Marsden, B. D., Kelm, S., Shi, J., Deane, C. M., et al. (2017) · Nature Communications · doi:10.1038/ncomms15123 · Cited by 314
Targeting MLL1 H3K4 Methyltransferase Activity in Mixed-Lineage Leukemia
Cao, F., Townsend, E. C., Karataş, H., Xu, J., Li, L., Lee, S. H. F., Liu, L., Chen, Y., Ouillette, P. D., Zhu, J., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2013.12.001 · Cited by 306
Regulation of eukaryotic translation by the RACK1 protein: a platform for signalling molecules on the ribosome
Nilsson, J., Sengupta, J., Frank, J., & Nissen, P. (2004) · EMBO Reports · doi:10.1038/sj.embor.7400291 · Cited by 296
The histone chaperone CAF-1 safeguards somatic cell identity
Cheloufi, S., Elling, U., Hopfgartner, B., Jung, Y. L., Murn, J., Ninova, M., Hubmann, M., Badeaux, A. I., Ang, C. E., Tenen, D. E., et al. (2015) · Nature · doi:10.1038/nature15749 · Cited by 291
Marked for death: Targeting epigenetic changes in cancer
Pfister, S. X., & Ashworth, A. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.256 · Cited by 288
Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia
Grebien, F., Vedadi, M., Getlik, M., Giambruno, R., Grover, A., Avellino, R., Skucha, A., Vittori, S., Kuznetsova, E., Smil, D., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1859 · Cited by 284
Self-citation
Structure of DDB1 in Complex with a Paramyxovirus V Protein: Viral Hijack of a Propeller Cluster in Ubiquitin Ligase
Li, T., Chen, X., Garbutt, K. C., Zhou, P., & Zheng, N. (2006) · Cell · doi:10.1016/j.cell.2005.10.033 · Cited by 259
Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C
Sackton, K. L., Dimova, N., Zeng, X., Tian, W., Zhang, M., Sackton, T. B., Meaders, J., Pfaff, K. L., Sigoillot, F., Yu, H., et al. (2014) · Nature · doi:10.1038/nature13660 · Cited by 257
MLL-AF9-Induced Leukemogenesis Requires Coexpression of the Wild-Type Mll Allele
Thiel, A. T., Blessington, P., Zou, T., Feather, D., Wu, X., Yan, J., Zhang, H., Liu, Z., Ernst, P., Koretzky, G. A., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.034 · Cited by 249
Structural basis for distinctive recognition of fibrinogen γC peptide by the platelet integrin αIIbβ3
Springer, T. A., Zhu, J., & Xiao, T. S. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200801146 · Cited by 243
Structural basis for activity regulation of MLL family methyltransferases
Li, Y., Han, J., Zhang, Y., Cao, F., Liu, Z., Li, S., Wu, J., Hu, C., Wang, Y., Jin, S., et al. (2016) · Nature · doi:10.1038/nature16952 · Cited by 243
Venetoclax: First Global Approval
Deeks, E. D. (2016) · Drugs · doi:10.1007/s40265-016-0596-x · Cited by 240
Increased LIS1 expression affects human and mouse brain development
Bi, W., Sapir, T., Shchelochkov, O. A., Zhang, F., Withers, M. A., Hunter, J. V., Levy, T., Shinder, V., Peiffer, D. A., Gunderson, K. L., et al. (2009) · Nature Genetics · doi:10.1038/ng.302 · Cited by 228
Affinity selection-mass spectrometry screening techniques for small molecule drug discovery
Annis, D. A., Nickbarg, E., Yang, X., Ziebell, M. R., & Whitehurst, C. E. (2007) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2007.07.011 · Cited by 226
The EED protein–protein interaction inhibitor A-395 inactivates the PRC2 complex
He, Y., Selvaraju, S., Curtin, M. L., Jakob, C. G., Zhu, H., Comess, K. M., Shaw, B., The, J., Lima-Fernandes, E., Szewczyk, M. M., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2306 · Cited by 224
Self-citation
Erratum: Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia
Grebien, F., Vedadi, M., Getlik, M., Giambruno, R., Grover, A., Avellino, R., Skucha, A., Vittori, S., Kuznetsova, E., Smil, D. V., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio1015-815b · Cited by 206
Self-citation
CDC20, a potential cancer therapeutic target, is negatively regulated by p53
Kidokoro, T., Tanikawa, C., Furukawa, Y., Katagiri, T., Nakamura, Y., & Matsuda, K. (2007) · Oncogene · doi:10.1038/sj.onc.1210799 · Cited by 206
LRRK2 Parkinson disease mutations enhance its microtubule association
Kett, L. R., Boassa, D., Ho, C. C., Rideout, H. J., Hu, J., Terada, M., Ellisman, M. H., & Dauer, W. T. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr526 · Cited by 200
RACK1 Controls IRES-Mediated Translation of Viruses
Majzoub, K., Hafirassou, M. L., Meignin, C., Goto, A., Marzi, S., Fedorova, A. A., Verdier, Y., Vinh, J., Hoffmann, J. A., Martin, F., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.041 · Cited by 195
A TGFβ-PRMT5-MEP50 axis regulates cancer cell invasion through histone H3 and H4 arginine methylation coupled transcriptional activation and repression
Chen, H., Lorton, B. M., Gupta, V., & Shechter, D. (2016) · Oncogene · doi:10.1038/onc.2016.205 · Cited by 188
Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells
Saenz, D. T., Fiskus, W. C., Qian, Y., Manshouri, T., Rajapakshe, K., Raina, K., Coleman, K. G., Crew, A. P. A., Shen, A., Mill, C. P., et al. (2017) · Leukemia · doi:10.1038/leu.2016.393 · Cited by 187
The many blades of the β-propeller proteins: conserved but versatile
Chen, C. K.-M., Chan, N., & Wang, A. H. ‐. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.07.004 · Cited by 185
Recruitment of Phosphorylated Chromatin Assembly Factor 1 to Chromatin after UV Irradiation of Human Cells
Martini, E. M.-D., Roche, D. M. J., Marheineke, K., Verreault, A., & Almouzni, G. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.3.563 · Cited by 182
Small-molecule inhibition of MLL activity by disruption of its interaction with WDR5
Senisterra, G. A., Wu, H. Y., Allali‐Hassani, A., Wasney, G. A., Baršytė-Lovejoy, D., Dombrovski, L., Dong, A., Nguyen, K. T., Smil, D. V., Bolshan, Y., et al. (2012) · Biochemical Journal · doi:10.1042/bj20121280 · Cited by 165
Self-citation
Identification of EZH2 and EZH1 Small Molecule Inhibitors with Selective Impact on Diffuse Large B Cell Lymphoma Cell Growth
Garapaty, S., Nasveschuk, C. G., Gagnon, A., Chan, E. Y., Sandy, P., Busby, J., Balasubramanian, S., Campbell, R., Zhao, F., Bergeron, L., et al. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2013.09.013 · Cited by 159
An allosteric inhibitor of substrate recognition by the SCFCdc4 ubiquitin ligase
Orlicky, S. M., Tang, X., Neduva, V., Elowe, N. H., Brown, E. D., Sicheri, F., & Tyers, M. (2010) · Nature Biotechnology · doi:10.1038/nbt.1646 · Cited by 150
Self-citation
Development of secondary mutations in wild-type and mutant EZH2 alleles cooperates to confer resistance to EZH2 inhibitors
Gibaja, V, Shen, F., Harari, J., Korn, J., Ruddy, D., Saenz-Vash, V, Zhai, H., Rejtar, T., Paris, C. G., Yu, Z., et al. (2016) · Oncogene · doi:10.1038/onc.2015.114 · Cited by 149
Structural basis of lentiviral subversion of a cellular protein degradation pathway
Schwefel, D., Groom, H. C. T., Boucherit, V., Christodoulou, E., Walker, P. A., Stoye, J. P., Bishop, K. N., & Taylor, I. A. (2013) · Nature · doi:10.1038/nature12815 · Cited by 133
Structural and Biochemical Insights into MLL1 Core Complex Assembly
Avdic, V., Zhang, P., Lanouette, S., Groulx, A. F., Tremblay, V., Brunzelle, J. S., & Couture, J. (2011) · Structure · doi:10.1016/j.str.2010.09.022 · Cited by 117
The WD40 Domain Is Required for LRRK2 Neurotoxicity
Jorgensen, N. D., Peng, Y., Ho, C. C., Rideout, H. J., Petrey, D. S., Liu, P., & Dauer, W. T. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008463 · Cited by 116
A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells
Mao, D. D., Gujar, A. D., Mahlokozera, T., Chen, I., Pan, Y., Luo, J. R., Brost, T. M., Thompson, E. A., Turski, A., Leuthardt, E. C., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.05.027 · Cited by 113
JAK2 rearrangements, including the novel SEC31A-JAK2 fusion, are recurrent in classical Hodgkin lymphoma
Roosbroeck, K. V., Cox, L., Tousseyn, T., Lahortiga, I., Gielen, O., Cauwelier, B., Paepe, P. D., Verhoef, G. E. G., Marynen, P., Vandenberghe, P., et al. (2011) · Blood · doi:10.1182/blood-2010-06-291310 · Cited by 111
Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy
Huang, Y. R., Zhang, J., Yu, Z., Zhang, H., Wang, Y., Lingel, A., Qi, W., Gu, J., Zhao, K., Shultz, M. D., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01576 · Cited by 105
ALK-positive large B-cell lymphomas with cryptic SEC31A-ALK and NPM1-ALK fusions
Roosbroeck, K. V., Cools, J., Dierickx, D., Thomas, J., Vandenberghe, P., Stul, M. S., Delabie, J., Wolf‐Peeters, C. D., Marynen, P., & Włodarska, I. (2010) · Haematologica · doi:10.3324/haematol.2009.014761 · Cited by 104
The DDB1–DCAF1–Vpr–UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction
Wu, Y., Zhou, X., Barnes, C. O., DeLucia, M., Cohen, A. E., Gronenborn, A. M., Ahn, J., & Calero, G. A. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3284 · Cited by 104
Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1)
Getlik, M., Smil, D. V., Zepeda‐Velázquez, C., Bolshan, Y., Poda, G. I., Wu, H. Y., Dong, A., Kuznetsova, E., Marcellus, R. C., Senisterra, G. A., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01630 · Cited by 94
Self-citation
A chemical probe toolbox for dissecting the cancer epigenome
Shortt, J., Ott, C. J., Johnstone, R. W., & Bradner, J. E. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.148 · Cited by 94
Novel LRRK2 GTP-binding inhibitors reduced degeneration in Parkinson's disease cell and mouse models
Li, T., Yang, D., Zhong, S., Thomas, J. M., Xue, F., Liu, J., Kong, L., Voulalas, P. J., Hassan, H. E., Park, J.-S., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu341 · Cited by 87
WDSPdb: a database for WD40-repeat proteins
Wang, Y., Hu, X.-J., Zou, X., Wu, X., Ye, Z., & Wu, Y. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1023 · Cited by 83
Acquisition of a single EZH2 D1 domain mutation confers acquired resistance to EZH2-targeted inhibitors
Baker, T. E., Nerle, S., Pritchard, J. R., Zhao, B., Rivera, V. M., Garner, A. P., & Gonzalvez, F. (2015) · Oncotarget · doi:10.18632/oncotarget.5066 · Cited by 80
MLL1 Inhibition Reprograms Epiblast Stem Cells to Naive Pluripotency
Zhang, H., Gayen, S., Xiong, J., Zhou, B. O., Shanmugam, A. K., Sun, Y., Karataş, H., Liu, L., Rao, R. C., Wang, S., et al. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.02.004 · Cited by 75
Initial testing (stage 1) of the PARP inhibitor BMN 673 by the pediatric preclinical testing program: PALB2 mutation predicts exceptional in vivo response to BMN 673
Smith, M. A., Hampton, O. A., Reynolds, C. P., Kang, M. H., Maris, J. M., Gorlick, R. G., Kolb, E. A., Lock, R. B., Carol, H., Keir, S. T., et al. (2014) · Pediatric Blood & Cancer · doi:10.1002/pbc.25201 · Cited by 74
Synthesis, Optimization, and Evaluation of Novel Small Molecules as Antagonists of WDR5-MLL Interaction
Bolshan, Y., Getlik, M., Kuznetsova, E., Wasney, G. A., Hajian, T., Poda, G. I., Nguyen, K. T., Wu, H. Y., Dombrovski, L., Dong, A., et al. (2013) · ACS Medicinal Chemistry Letters · doi:10.1021/ml300467n · Cited by 74
Self-citation
Intragenic deletions and duplications of the LIS1 and DCX genes: a major disease-causing mechanism in lissencephaly and subcortical band heterotopia
Haverfield, E. V., Whited, A. J., Petras, K. S., Dobyns, W. B., & Das, S. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.213 · Cited by 73
Retinoblastoma Binding Protein 4 Modulates Temozolomide Sensitivity in Glioblastoma by Regulating DNA Repair Proteins
Kitange, G. J., Mladek, A. C., Schroeder, M. A., Pokorny, J. C., Carlson, B. L., Zhang, Y., Nair, A., Lee, J., Yan, H., Decker, P. A., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.02.045 · Cited by 73
Gene expression profiling in glioblastoma and immunohistochemical evaluation of IGFBP-2 and CDC20
Marucci, G., Morandi, L., Magrini, E., Farnedi, A., Franceschi, E., Miglio, R., Calò, D. G., Pession, A., Foschini, M. P., & Eusebi, V. (2008) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-008-0685-7 · Cited by 71
The GNB3 C825T polymorphism as a pharmacogenetic marker in the treatment of hypertension, obesity, and depression
Klenke, S., Kussmann, M., & Siffert, W. (2011) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e3283491153 · Cited by 63
Co-repressor complexes and remodelling chromatin for repression
Wolffe, A. P., Urnov, F. D., & Guschin, D. Y. (2000) · Biochemical Society Transactions · doi:10.1042/bst0280379 · Cited by 61
VprBP Has Intrinsic Kinase Activity Targeting Histone H2A and Represses Gene Transcription
Kim, K., Kim, J., Kim, J., Choi, J., Lee, Y. S., Neamati, N., Song, J. S., Heo, K., & An, W. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.09.017 · Cited by 61
A Method for WD40 Repeat Detection and Secondary Structure Prediction
Wang, Y., Jiang, F., Zhuo, Z., Wu, X., & Wu, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065705 · Cited by 57
CDC20 maintains tumor initiating cells
Xie, Q., Wu, Q., Mack, S. C., Yang, K., Kim, L., Hubert, C. G., Flavahan, W. A., Chu, C., Bao, S., & Rich, J. N. (2015) · Oncotarget · doi:10.18632/oncotarget.3676 · Cited by 55
Preclinical target validation using patient-derived cells
Edwards, A. M., Arrowsmith, C. H., Bountra, C., Bunnage, M. E., Feldmann, M., Knight, J. C., Patel, D. D., Prinos, P., Taylor, M. D., Sundström, M., et al. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4565 · Cited by 54
Self-citation
Discovery and Molecular Basis of a Diverse Set of Polycomb Repressive Complex 2 Inhibitors Recognition by EED
Li, L., Zhang, H., Zhang, M., Zhao, M., Feng, L., Luo, X., Gao, Z., Huang, Y. R., Ardayfio, O., Zhang, J.-H., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0169855 · Cited by 54
The scaffold protein RACK1 mediates the RANKL-dependent activation of p38 MAPK in osteoclast precursors
Lin, J., Lee, D., Choi, Y., & Lee, S. Y. (2015) · Science Signaling · doi:10.1126/scisignal.2005867 · Cited by 49
Structural basis for streptogramin B resistance in Staphylococcus aureus by virginiamycin B lyase
Korczynska, M., Mukhtar, T. A., Wright, G. D., & Berghuis, A. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701809104 · Cited by 46
Unclosed β-Propellers Display Stable Structures: Implications for Substrate Access to the Active Site of Prolyl Oligopeptidase
Juhász, T., Szeltner, Z., Fülöp, V., & Polgár, L. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.12.014 · Cited by 42
Cytogenetically complex SEC31A-ALK fusions are recurrent in ALK-positive large B-cell lymphomas
Bedwell, C., Rowe, D. W., Moulton, D., Jones, G., Bown, N. P., & Bacon, C. M. (2010) · Haematologica · doi:10.3324/haematol.2010.031484 · Cited by 39
Structural basis for a class of nanomolar influenza A neuraminidase inhibitors
Kerry, P. S., Mohan, S., Russell, R. J. M., Bance, N., Niikura, M., & Pinto, B. M. (2013) · Scientific Reports · doi:10.1038/srep02871 · Cited by 37
An allosteric conduit facilitates dynamic multisite substrate recognition by the SCFCdc4 ubiquitin ligase
Csizmók, V., Orlicky, S. M., Cheng, J., Song, J., Bah, A., Delgoshaie, N., Lin, H., Mittag, T., Sicheri, F., Chan, H. S., et al. (2017) · Nature Communications · doi:10.1038/ncomms13943 · Cited by 36
Self-citation
Mouse model implicates GNB3 duplication in a childhood obesity syndrome
Goldlust, I. S., Hermetz, K. E., Catalano, L. M., Barfield, R., Cozad, R., Wynn, G. M., Ozdemir, A. C., Conneely, K. N., Mullé, J. G., Dharamrup, S., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305999110 · Cited by 32
SAR of amino pyrrolidines as potent and novel protein-protein interaction inhibitors of the PRC2 complex through EED binding
Curtin, M. L., Pliushchev, M. A., Li, H., Torrent, M., Dietrich, J. D., Jakob, C. G., Zhu, H., Zhao, H., Wang, Y., Ji, Z., et al. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.02.030 · Cited by 30
Self-citation
Integrating population variation and protein structural analysis to improve clinical interpretation of missense variation: application to the WD40 domain
Laskowski, R. A., Tyagi, N., Johnson, D. S., Joss, S. K., Kinning, E., McWilliam, C., Splitt, M. P., Thornton, J. M., Firth, H. V., Study, T. D., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddv625 · Cited by 29

Sorted by citations

Targeted 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
Self-citation
Epigenetic tools (The Writers, The Readers and The Erasers) and their implications in cancer therapy
Biswas, S., & Rao, C. M. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.08.021 · Cited by 442
Imidazoles as Potential Anticancer Agents: An Update on Recent Studies
Sharma, P., LaRosa, C., Antwi, J., Govindarajan, R., & Werbovetz, K. A. (2021) · Molecules · doi:10.3390/molecules26144213 · Cited by 220
Targeting G protein-coupled receptor signalling by blocking G proteins
Campbell, A. P., & Smrcka, A. V. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.135 · Cited by 201
A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models
Yu, X., Li, D., Kottur, J., Shen, Y., Kim, H. S., Park, K., Tsai, Y., Gong, W., Wang, J., Suzuki, K., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abj1578 · Cited by 149

See all 346

Authors: Schapira, M., Tyers, M., Torrent, M., & Arrowsmith, C. H.
Affiliations: University of Toronto (CA)
Mount Sinai Hospital (CA)
AbbVie (United States) (US)
Corresponding author: Schapira, Matthieu
ORCID: Schapira, Matthieu
Tyers, Mike
Arrowsmith, Cheryl H.
Venue: Nature Reviews Drug Discovery
Publisher: Springer Science and Business Media LLC
Published: 2017-10-13
Volume: 16
Issue: 11
Pages: 773-786
ISSN: 1474-1776 (ISSN-L)
1474-1784
DOI: 10.1038/nrd.2017.179
PMC: PMC5975957
OpenAlex: W2761872853
Cited by: 335
References: 124
Citations by year: 2026: 33 · 2025: 40 · 2024: 54 · 2023: 50 · 2022: 43 · 2021: 50 · 2020: 28 · 2019: 22 · 2018: 15
FWCI: 1.66
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Drug Discovery (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Genome Canada
Wellcome Trust
Ontario Genomics Institute
National Institutes of Health (R01OD010929)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
Keywords: WD40 repeat domain, WDR5, EED, protein-protein interaction inhibitors, small molecule drug discovery, beta-propeller proteins, peptide binding pocket, druggability, chromatin regulation
MeSH terms: WD40 Repeats, Animals, Humans, Molecular Targeted Therapy

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

WD40 repeat domain proteins: a novel target class?

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks