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

Flagged first, then by citations

Show all 124 references

Sorted by citations

Items 201–300 of 346

WDR36 Safeguards Self-Renewal and Pluripotency of Human Extended Pluripotent Stem Cells
An, S., Yao, D., Zhang, W., Sun, H., Yu, T., Ruizhe, J., & Yang, Y. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.905395 · Cited by 4
“These structural domains are important subunits of multiprotein complexes involved in multiple signaling pathways, such as DNA damage sensing and repair, epigenetic regulation of gene expression and chromatin organization, ubiquitin signaling and protein degradation, cell cycle, and immune-related pathways (Schapira e…”
Background
Utilizing an artificial intelligence system to build the digital structural proteome of reef-building corals
(2022) · doi:10.1093/gigascience/giac117 · Cited by 4
“WD40 repeats with a “doughnut hole” usually serve as protein interaction scaffolds in multiprotein complexes [34], which might also regulate innate immunity and stress response [35, 36].”
Bioinformatics and gene expression analysis of the legume F-box/WD40 proteins in NaCl and high temperature stress
Çelik, H., Aravena, A., & Kara, N. T. (2023) · Genetic Resources and Crop Evolution · doi:10.1007/s10722-023-01592-x · Cited by 4
The Neurobeachin‐like 2 protein ( NBEAL2 ) controls the homeostatic level of the ribosomal protein RPS6 in mast cells
Wegner, P., Drube, J., Ziegler, L., Strotmann, B., Marquardt, R., Küchler, C., Groth, M., Nieswandt, B., Andreas, N., & Drube, S. (2024) · Immunology · doi:10.1111/imm.13756 · Cited by 4
“WDR domain-containing proteins play an important role in protein degradation processes [37].”
Background
Fighting Cancer Stem Cell Fate by Targeting LIS1 a WD40 Repeat Protein
Brehar, F. M., Dragomir, M. P., Petrescu, G. E. D., & Gorgan, R. M. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01142 · Cited by 4
“Also, LIS1 contains one of the most encountered protein interactions domain in human, the WD40 repeat domain (41), incorporating in its structure seven WD40 repeats (38).”
Background
WDR34 affects PI3K/Akt and Wnt/β-catenin pathways to regulates malignant biological behaviors of glioma cells
Zuo, J., Liu, C., Ni, H., & Yu, Z. (2022) · Journal of Neuro-Oncology · doi:10.1007/s11060-021-03932-2 · Cited by 5
“It has been well-documented that WDR proteins participate in the regulation of a variety of cellular processes, and perturbations in these proteins are involved in human malignancies [18].”
Background
CoRe: A robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screensPreprint
Vinceti, A., Karakoc, E., Pacini, C., Perron, U., Lucia, R. R. D., Garnett, M. J., & Iorio, F. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.25.445610 · Cited by 4
Targeted protein degradation in pancreatic cancer: advances and challenges of PROTAC-based therapeutics
Huang, M., Wei, F., Cao, J., & Jiang, H. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.108985 · Cited by 4
In Silico Exploration of Anti‐Cancer Phytochemicals as Novel Inhibitors of LRRK2 via the WDR Domain
Umar, H. I., Alshehri, M. M., Alaqarbeh, M., Omoboyede, V., Hassan, T. A., Bello, R. O., Ahmad, A. F., Odetayo, I. K., Alanazi, A., Alqarni, Y. S., et al. (2025) · ChemistrySelect · doi:10.1002/slct.202503726 · Cited by 3
A distinct PP2A subunit regulates local protein phosphorylation at the axon initial segment
Anderson, A. P., Kim, S., Melton, A. J., Ding, X., Zhang, W., Saltzman, A. B., Malovannaya, A., Rasband, M., & Gao, Y.-D. (2025) · Nature Communications · doi:10.1038/s41467-025-66120-0 · Cited by 3
Structural characterization of endogenous microprotein EMBOW reveals an alternative MRT motif for WDR5 ‐interacting site recognition
Yang, Y., Pan, Y., Zhang, S., Wang, H., Sun, X., Hang, T., & Xu, L. (2026) · FEBS Journal · doi:10.1111/febs.70450 · Cited by 3
“Consequently, targeting to disrupt WDR5 interactions by mimicking the WIN motif has emerged as a promising therapeutic strategy, with WIN site-targeting inhibitors showing potential in pre-clinical cancer models [19,29,36].”
WD repeat domain 5 (WDR5) inhibitors: a patent review (2016-present)
Coker, J. A., & Stauffer, S. R. (2024) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2024.2441658 · Cited by 4
“WDR-containing proteins have historically been considered challenging, if not undruggable, targets [49–51].”
Identification of Novel Genetic Variants in a Cohort of Congenital Hypogonadotropic Hypogonadism: Computational Analysis of Pathogenicity Predictions
Chiarello, P., Gualtieri, G., Bossio, S., Seminara, G., Molinaro, M., Antonucci, G., Perri, A., Rocca, V., Cannarella, R., Vignera, S. L., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26115207 · Cited by 5
“The β -propeller fold of these domains is structurally adaptable, allowing the domain to maintain its integrity despite deletion or insertion of WD repeats, which can range from 5 to 8 repeats [7].”
Potential Resistance to Antineoplastic Aminated Fullerenes Mediated by M2-Like Monocyte-Derived Exosomes
Huo, J., Zhou, W., Liu, Y., Yang, S., Li, J., & Wang, C. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.779939 · Cited by 3
“org 5 coupled receptor (GPCR) signaling, DNA damage sensing and repair, the ubiquitin-proteasome system (UPS), cell growth and division, epigenetic regulation of gene expression and chromatin organization, and the immune system (35).”
Background
Epidemiological, Clinical, and Genomic Profile in Head and Neck Cancer Patients and Their Families
Chulam, T. C., Bertonha, F. B., Villacis, R. A. R., Filho, J. G., Kowalski, L. P., & Rogatto, S. R. (2022) · Biomedicines · doi:10.3390/biomedicines10123278 · Cited by 3
“WDR proteins have been associated with cancer development [34].”
Background
A screen for MeCP2-TBL1 interaction inhibitors using a luminescence-based assay
Alexander-Howden, B., Zhang, L., van der Sloot, A. M., Tollis, S., St‐Cyr, D. J., Sicheri, F., Bird, A. P., Tyers, M., & Lyst, M. J. (2023) · Scientific Reports · doi:10.1038/s41598-023-29915-z · Cited by 3
Self-citation
Characterization of Tau95 led to the identification of a four-subunit TFIIIC complex in trypanosomatid parasites
Mondragón-Rosas, F., Florencio-Martínez, L. E., Villa-Delavequia, G. S., Manning-Cela, R. G., Carrero, J. C., Nepomuceno‐Mejía, T., & Martínez‐Calvillo, S. (2024) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-023-12903-8 · Cited by 3
“Both Tau60 and Tau91 are characterized by the presence of WD40 repeats (Mylona et al. 2006), which are commonly seven-bladed β-propeller domains with an overall doughnut shape that participate in protein-protein interactions (Schapira et al. 2017).”
Genetic architecture of preeclampsia
Manoharan, A., Ballambattu, V. B., & Palani, R. S. (2024) · Clinica Chimica Acta · doi:10.1016/j.cca.2024.119656 · Cited by 4
WDR64, a testis-specific protein, is involved in the manchette and flagellum formation by interacting with ODF1
Zhang, Y., Xing, X., Huang, L., Su, Y., Liu, G., Zhang, X., & Yang, Y. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e38263 · Cited by 3
“…have been annotated and these proteins are involved in a broad range of biological functions, including DNA damage sensing and repair, epigenetic regulation of gene expression and chromatin organization, cell cycle regulation, signal transduction, and cilia and flagella assembly pathways [8 – 10].”
Genetic Effects on Dispersion in Urinary Albumin and Creatinine in Three House Mouse (Mus musculus) Cohorts
Perry, G. M. L. (2019) · G3 Genes Genomes Genetics · doi:10.1534/g3.118.200940 · Cited by 3
Структурные, функциональные и эволюционные характеристики белков с повторами
Deryusheva, E. I., Валериевич, М. А., & Галзитская, О. В. (2021) · Molecular Biology · doi:10.31857/s0026898421050037 · Cited by 3
Plasmodium falciparum contains functional SCF and CRL4 ubiquitin E3 ligases, and CRL4 is critical for cell division and membrane integrityPreprint
Rizvi, Z., Reddy, G. S., Gorde, S. M., Pundir, P., Das, D., & Sijwali, P. S. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.18.537323 · Cited by 3
Enrichment of Cysteine S-palmitoylated peptides using Sodium Deoxycholate Acid Precipitation - SDC-ACEPreprint
Jensen, P. T., Palmisano, G., Rhodes, C. J., & Larsen, M. R. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.09.548252 · Cited by 3
ATG8 in single membranes: Fresh players of endocytosis and acidic organelle quality control in cancer, neurodegeneration, and inflammation
Ben, W. B., & Apaja, P. M. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.151384 · Cited by 2
Characterization of the WD40 gene family in Pyrus bretschneideri and functional analysis of PbrWD40–60 in pollen tube growth
Li, M., Yan, Y., Zhou, J., Dai, Y., Wu, J., Zhang, S., & Kou, X. (2025) · Scientia Horticulturae · doi:10.1016/j.scienta.2025.114183 · Cited by 2
Isotopologues of a Metabolic Precursor for Selective N-15 and C-13 Histidine Labeling
Brüschweiler, S., Hlavac, M., Kratzwald, S. E., Schörghuber, J., Siess, K. M., Wimmer, A., Platzer, G., Konrat, R., & Lichtenecker, R. J. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169347 · Cited by 2
Discovering Uncharted Binding Pockets on E3 Ligases Leads to the Identification of FBW7 Allosteric Modulators
Martínez‐Cartró, M., Serrano‐Morrás, Á., Bertran‐Mostazo, A., Castaño‐Muñiz, R., Scaffidi, S., Ivanova, V., Csorba, N., Simon, J., Ábrányi‐Balogh, P., Li, Y., et al. (2025) · Advanced Science · doi:10.1002/advs.202506068 · Cited by 2
Enrichment of Cysteine S-palmitoylated Peptides Using Sodium Deoxycholate Acid Precipitation
Jensen, P. T., Palmisano, G., Rhodes, C. J., & Larsen, M. R. (2025) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2025.101218 · Cited by 2
“This domain consists of a central pore formed by circularly arranged beta-propeller folds, often acting as interaction scaffold proteins within multiprotein complexes (76).”
Cost-effective non-additive GWAS across 2329 diseases in 500,349 individuals
Molotkov, I., Kurki, M., FinnGen, Palotie, A. V., Daly, M. J., & Artomov, M. (2025) · Nature Communications · doi:10.1038/s41467-025-67277-4 · Cited by 2
“WDR55 is part of the WD-repeat domain family, genes from which are explored as a novel drug target class 30 .”
A periplasmic protein complex mediates arabinofuranosyltransferase activity and intrinsic drug resistance in Mycobacterium tuberculosis
Klevorn, T., Brown, C. D., Hardy, C. D., Cuthbert, B. J., Spencer, A., Jinich, A., Chan, L., Angala, S. K., Manzer, J., Mendoza, J., et al. (2026) · Science Advances · doi:10.1126/sciadv.aec5100 · Cited by 2
“Rv3035 is annotated as an essential hypothetical protein containing WD40 repeats that are predicted to form an eight-bladed β - propeller scaffold—a structural motif that mediates protein-protein interactions and multiprotein complex assembly in prokaryotes and eukaryotes ( 10 ).”
RACK1: A multifunctional scaffold protein involved in signal transduction, ribosomal regulation, and Cancer pathogenesis
Yang, J.-C., Du, Y.-Y., Zuo, W., Yao, J.-Y., Ma, K., Liang, Y. J., Zhao, M., & Li, Z.-M. (2026) · Cellular Signalling · doi:10.1016/j.cellsig.2026.112519 · Cited by 2
Antibacterial drug discovery: challenges and preclinical promises from synthetic small molecules
Fernandes, G., Kim, S., dos Santos, J. L., Wang, Y., Soudy, C., Redmond, J. M., Castagnolo, D., & Todd, M. H. (2026) · Chemical Society Reviews · doi:10.1039/d5cs00617a · Cited by 4
Genome wide identification and analysis of WD40 domain containing proteins in Danio rerio
Afza, F., Singh, N., Shriya, S., Bisoyi, P., Kashyap, A. K., & Jain, B. P. (2021) · Gene Reports · doi:10.1016/j.genrep.2021.101426 · Cited by 2
ProxyBind: A compendium of binding sites for proximity-induced pharmacology
Rovers, E., Liu, L., & Schapira, M. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.11.010 · Cited by 3
“Five kinases contain a WD-40 repeat (WDR), which is a b -propeller domain with a druggable central cavity [30].”
BackgroundSelf-citation
Systematic genetic identification of functional domains on collided di‐ribosomes responsible for rescue pathways upon translation arrest in Saccharomyces cerevisiae
Otsuka, H., Endo, K., WADA, M., & Ito, K. (2023) · FEBS Journal · doi:10.1111/febs.16781 · Cited by 2
JNK‐interacting protein 4 is a central molecule for lysosomal retrograde trafficking
Sasazawa, Y., Hattori, N., & Saiki, S. (2023) · BioEssays · doi:10.1002/bies.202300052 · Cited by 2
“Although the WD40 repeat domainactsasaproteininteractionscaffoldinmultiproteincomplexes in general [41] , its importance for JIP3 and JIP4 functions remains uninvestigated.”
WD40 Protein NLE1 as a Novel Diagnostic Biomarker Promoting Hepatocellular Carcinoma Proliferation
Zhang, R.-T., Liu, D.-H., Feng, X.-X., Yang, Z.-Y., & Zhang, K.-G. (2025) · Clinical Medicine Insights: Oncology · doi:10.1177/11795549251348902 · Cited by 2
“6 In this study, we focused on the expression and characterisation of WD40 proteins in HCC. 36-39 PAM has been reported to be correlated with liver cancer prognosis in previous studies.”
Global characterization of proteome and lysine methylome features in EZH2 wild-type and mutant lymphoma cell lines
Hao, B., Sun, M., Zhang, M., Zhao, X., Zhao, L., Li, B., Zhai, L., Liu, P., Hu, H., Xu, J., et al. (2019) · Journal of Proteomics · doi:10.1016/j.jprot.2019.103614 · Cited by 2
Structure Based Design of Bicyclic Peptide Inhibitors of RbAp48
Hart, P. ‘., Hommen, P., Noisier, A. F. M., Krzyzanowski, A., Schüler, D., Porfetye, A. T., Akbarzadeh, M., Vetter, I. R., Adihou, H., & Waldmann, H. (2020) · Angewandte Chemie · doi:10.1002/ange.202009749 · Cited by 2
The First CACHE Challenge – Identifying Binders of the WD-Repeat Domain of Leucine-Rich Repeat Kinase 2Preprint
Patrascu, M. B., Nivedha, A. K., Rostaing, O., Chukka, P., Moitessier, N., & Pottel, J. (2022) · ChemRxiv · doi:10.26434/chemrxiv-2022-ncqsj · Cited by 2
The Quest for Stability during Times of Change
Justman, Q. A. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.05.005 · Cited by 1
CqPP2A inhibits white spot syndrome virus infection by up-regulating antimicrobial substances expression in red claw crayfish Cherax quadricarinatus
Gao, R.-L., Liu, L.-K., Li-mei, G., Wang, K., & Liu, H. (2020) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2020.103913 · Cited by 1
Independent and Complementary Functions of Caf1b and Hir1 for Chromatin Assembly in Tetrahymena thermophila
Hao, H., Ren, C., Lian, Y., Zhao, M., Bo, T., Xu, J., & Wang, W. (2023) · Cells · doi:10.3390/cells12242828 · Cited by 1
“WD domains serve as crucial subunits within multiprotein complexes involved in diverse signaling pathways [44].”
Background
Woodhouse-Sakati syndrome: genotype–phenotype review and case of intra-familial heterogeneity
Wakim, V., Dassouki, M. E., Azar, A., Hani, A. J., Mehawej, C., Chouery, É., Baroudi, M.-J., & Wakim, G. (2024) · Journal of Rare Diseases · doi:10.1007/s44162-024-00045-y · Cited by 1
“This conserved region helps bind to damage DNA binding 1 (DDB1) protein which has been linked to multi-systemic diseases involving neurological, endocrinological, and overall oncologic systems [28, 35, 39].”
Exploring the Potential of Homologous Recombination Protein PALB2 in Synthetic Lethal Combinations
Lu, X., Sauter, B., Keller, A., Zhanybekova, S., & Gillingham, D. G. (2025) · ACS Chemical Biology · doi:10.1021/acschembio.5c00111 · Cited by 1
Genetics and phenotypic heterogeneity of Galloway–Mowat syndrome
Huang, L., Wang, Y., Zhang, Y., Fu, H., & Mao, J. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02307-8 · Cited by 1
“WDR73 is expected to encode proteins containing six WD40 motifs, and WDR represents one of the most abundant domains in the human proteome [23], which is also present in other eukaryotes [24].”
Structural Basis for Non-classical WIN Peptides Recognition by WDR5
Yang, Y., Pan, Y., Wang, Q., Li, H., Zhang, S., Sun, X., Xia, L., Xu, L., & Chen, X. (2026) · Journal of Molecular Biology · doi:10.1016/j.jmb.2026.169666 · Cited by 1
WDR72 Is Required for Urinary Acidification and Normal H + ‐ ATPase Activity in Intercalated Cells in Mice
Auwerx, H., Busch‐Dohr, M., Li, X., Wagner, C. A., & Bourgeois, S. (2026) · Acta Physiologica · doi:10.1111/apha.70165 · Cited by 1
“Despite the well-documented general functions of several WD40 proteins [16], the precise biological role of WDR72 remains poorly understood.”
Wdr4 regulates ribosome biogenesis and intestinal homeostasis via let-7
Kajal, K., Rastegari, E., Wang, W., Li, J., Chen, C., Chou, W., Chang, W. C., Lin, T.-Y., Tsai, K., Lu, T.-M., et al. (2026) · EMBO Reports · doi:10.1038/s44319-026-00701-y · Cited by 1
“WD repeat domain 4 (Wdr4) encodes a conserved protein with ﬁ ve WD40 domains involved in protein-protein interactions (Schapira et al, 2017; Wu et al, 2006).”
Targeting WDR12 Unleashes T‐Cell‐Mediated Antitumor Activity in Melanoma by Destabilizing CD276
Pan, J., Chang, R., Zhang, M., Dong, Q., Zhang, G., Chen, X., Chen, M., Lu, L. Z.-B., Liang, X., Guo, Y., et al. (2026) · Advanced Science · doi:10.1002/advs.76255 · Cited by 1
“WD proteins contain highly conserved repeating units that are flanked by characteristic N-terminal GH (glycine-histidine) and C-terminal WD (tryptophan-aspartic acid) dipeptides [ 18 ].”
Extracellular and membrane-targeted protein degradation (emTPD): Mechanisms, design frameworks, and therapeutic opportunities
Zhang, K., Qiu, F., Lü, A., & Liang, C. (2026) · The Innovation Drug Discovery · doi:10.59717/j.xinn-drugdisc.2026.100024 · Cited by 1
Deleterious mutations in a heterozygous chromosome result in recessive lethality in silkworm semiconsomic strains
Tomihara, K., Tanaka, S., Katsuma, S., Shimada, T., Kobayashi, J., & Kiuchi, T. (2022) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2023.103933 · Cited by 1
Tle6 deficiency in male mice led to abnormal sperm morphology and reduced sperm motility
Kazama, K., Miyagoshi, Y., & Nishizono, H. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1481659 · Cited by 1
Identification of narciclasine as a novel NRF2 inhibitor
Ngo, H. H., Yu, B.-Y., Lee, J.-E., Kim, H. W., & Keum, Y. (2025) · Free Radical Research · doi:10.1080/10715762.2025.2451679 · Cited by 1
“…2). the tryptophan-aspartate repeat (WDR) domain proteins participate in a variety of cellular processes, including G protein-coupled receptor signaling, DNa damage perception and repair, the ubiquitin-proteasome system, the epigenetic regulation of chromatin, and immune system function [29].”
Pan-cancer analysis identifies EIPR1 as a potential prognostic and immunological biomarker for lung adenocarcinoma and its functional validation
Zheng, X. M., Zhang, X., Yu, J., & Zheng, J. (2025) · Gene · doi:10.1016/j.gene.2025.149439 · Cited by 1
RBAP48 facilitates the oral squamous cell carcinoma process in an androgen receptor-dependent and independent manners
Wang, X., Yan, G., Li, H., Wang, C., Kang, Y., Wang, S., Liu, W., Lin, L., Zou, R., Zeng, K., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-08215-4 · Cited by 1
“RBAP48 features a WD40-repeat structure that is speculated to act as a scaffold for protein-protein interactions in multiprotein complexes 26,27 .”
Application of fluorescent-based technology detecting protein-protein interactions to monitor the binding of hepatitis B virus X protein to DNA-damage-binding protein 1
Omagari, K., Asamitsu, K., & Tanaka, Y. (2021) · Biophysics and Physicobiology · doi:10.2142/biophysico.bppb-v18.008 · Cited by 1
“Some viral proteins associate with the DDB1-containing E3 ubiquitin ligase to degrade antiviral regulatory factors in host cells [10], with hepatitis B virus X protein (HBx) as one of the most well-known examples.”
Background
A Structural View on Druggability
Egner, U., & Hillig, R. C. (2020) · Wiley eBooks · doi:10.1002/9781118681121.ch2 · Cited by 1
Base editing derived models of human WDR34 and WDR60 disease alleles replicate retrograde IFT and hedgehog signaling defects and suggest disturbed Golgi protein transportPreprint
Antony, D., Güleç, E. Y., Bakey, Z., Schüle, I., Kim, G.-J., Skatulla, I., Brunner, H. G., Arnold, S. J., & Schmidts, M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.03.14.483768 · Cited by 1
Discovery of small molecule antagonists of human Retinoblastoma Binding Protein 4 (RBBP4)Preprint
Perveen, S., Zepeda‐Velázquez, C., McLeod, D., Marcellus, R. C., Mohammed, M., Abbey, M., Ensan, D., Panagopoulos, D., Trush, V. V., Gibson, E., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.05.475077 · Cited by 1
Self-citation
The First CACHE Challenge – Identifying Binders of the WD-Repeat Domain of Leucine-Rich Repeat Kinase 2Preprint
Patrascu, M. B., Nivedha, A. K., Rostaing, O., Chukka, P., Moitessier, N., & Pottel, J. (2022) · ChemRxiv · doi:10.26434/chemrxiv-2022-ncqsj-v2 · Cited by 1
Identification and study of Prolyl Oligopeptidases and related sequences in bacterial lineagesPreprint
Nayak, S. D., & Sowdhamini, R. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.22.614393 · Cited by 1
A periplasmic protein complex supports arabinofuranosyltransferase activity and mediates intrinsic drug resistance in Mycobacterium tuberculosisPreprint
Klevorn, T., Brown, C. D., Hardy, C. D., Cuthbert, B. J., Spencer, A., Jinich, A., Chan, L., Angala, S. K., Manzer, J., Mendoza, J., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.08.663683 · Cited by 1
“These domains can serve as scaffolds in protein-protein interactions and the formation of multiprotein complexes and play important roles in prokaryotes and eukaryotes ( 11 ).”
The Structural Basis for Pacs1-Wdr37 Complex Assembly and StabilityPreprint
Xiao, L., Grzemska, M. G., Pi, X., Chen, L., Turner, M., Peddada, N., Calvache, S., Jia, J., Beutler, B., Wu, H., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.05.686565 · Cited by 1
“Notably, recent work has identified the central pores of WD40 β-278 propellers as promising drug targets, with small molecules shown to engage and modulate the function of WDR proteins such as EED and WDR5 with nanomolar affinity 25, 26 .”
Absolute quantification of gene copy number variation in Plasmodium falciparum novel putative genes associated to drug resistance (the actin-binding coronin protein, cysteine desulfurase and plasmepsin 2), using Eva green-based quantitative PCRPreprint
Diarra, H., Mobegi, V. A., Makhulu, E. E., Kinyua, J., & Herren, J. K. (2022) · Research Square · doi:10.21203/rs.3.rs-1451928/v1 · Cited by 1
ARABIDOPSIS POLLEN ABORTION MUTANT 2, Encoding an Unknown Protein with Three WD40-Repeats, Is Essential for Late Pollen Mature in Arabidopsis thalianaPreprint
Ma, Z., Zhang, X., Chen, L., Zhang, G., Liu, Y., Ye, D., & Yang, H. (2019) · Research Square · doi:10.21203/rs.2.11828/v1
“When present in a protein, the WD40 motif is typically found as several (usually 4–10) tandem repeat units and they usually function as a protein– protein or protein–DNA/RNA interaction platform [2, 3, 4].”
Background
Elucidating the Regulatory Role of PHIP1 in Activated T Cell Metabolism and Immunity
Jain, S. (2019) · TSpace (University of Toronto)
Identification of candidate therapeutics and signaling pathways for multiple myelomaPreprint
Gu, H. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.03.467084
Structure-Based Survey of the Human Proteome for Opportunities in Proximity PharmacologyPreprint
Rovers, E., & Schapira, M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.13.475779
Self-citation
Mechanisms of Substrate Recognition by the Cul3-based E3 Ligase
Rebola, K. G. D. O. (2021) · doi:10.15760/etd.7721
ARABIDOPSIS POLLEN ABORTION MUTANT 2, Encoding an Unknown Protein with Three WD40-Repeats, Is Essential for Late Pollen Mature in Arabidopsis thalianaPreprint
Ma, Z., Zhang, X., Chen, L., Zhang, G., Liu, Y., Ye, D., & Yang, H. (2019) · Research Square · doi:10.21203/rs.2.11828/v2
Translation of Mycobacterium Survival Strategy to Develop a Lipo‐peptide based Fusion Inhibitor**
Sardar, A., Lahiri, A., Kamble, M., Mallick, A. I., & Tarafdar, P. K. (2020) · Angewandte Chemie · doi:10.1002/ange.202013848
Cockayne syndrome in an Iranian pedigree with a homozygous missense variant in the ERCC6 gene
Nikfar, A., Mansouri, M., Chiti, H., Abhari, G. F., & Parsamanesh, N. (2022) · Gene Reports · doi:10.1016/j.genrep.2022.101665
DRACC1, a major postsynaptic protein, regulates the condensation of postsynaptic proteins via liquid-liquid phase separationPreprint
Kaizuka, T., Hirouchi, T., Saneyoshi, T., Hayashi, Y., & Takumi, T. (2023) · bioRxiv · doi:10.1101/2023.01.23.525126
“…we also searched for proteins named after specific domains; Tmem for a transmembrane domain, Ccdc for a coiled-coil domain, Cctm for both of them, and Zfp for a zinc finger domain (Brayer and Segal, 2008; Marx et al., 2020; Priyanka and Yenugu, 2021; Schapira et al., 2017; Sohn et al., 2016).”
Background
Data from Loss-of-Function Mutations in TRAF7 and KLF4 Cooperatively Activate RAS-Like GTPase Signaling and Promote Meningioma Development
Najm, P., Zhao, P., Steklov, M. Y., Sewduth, R. N., Baietti, M. F., Pandolfi, S., Criem, N., Lechat, B., Maia, T. M., Haver, D. V., et al. (2023) · doi:10.1158/0008-5472.c.6513261.v1
Probing the DCAF12 interactions with MAGEA3 and CCT5 C-terminal degronsPreprint
Righetto, G. L., Yin, Y., Vu, V., Duda, D. M., Szewczyk, M. M., Zeng, H., Li, Y., Loppnau, P., Mei, T., Li, Y.-Y., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.15.553295
Germline gene fusions across species reveal the chromosomal instability regions and cancer susceptibility
Zhou, B., Wu, Q.-Q., Mauki, D. H., Wang, X., Zhang, S.-R., Yin, T., Chen, F., Li, C., Yan-hu, L., Wang, G., et al. (2023) · iScience · doi:10.1016/j.isci.2023.108431 · Cited by 1
The First CACHE Challenge – Testing Diverse Virtual Screening Scoring Methods to Identify Potential LRRK2 BindersPreprint
Patrascu, M. B., Nivedha, A. K., Rostaing, O., Chukka, P., Moitessier, A., Moitessier, N., & Pottel, J. (2024) · ChemRxiv · doi:10.26434/chemrxiv-2022-ncqsj-v3
Additional file 4 of WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer
Li, Z., Feng, M., Zhang, J., Wang, X., Xu, E., Wang, C., Lin, F., Yang, Z., Heng, Y., Guan, W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15139136
Additional file 10 of WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer
Li, Z., Feng, M., Zhang, J., Wang, X., Xu, E., Wang, C., Lin, F., Yang, Z., Heng, Y., Guan, W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15139112
Additional file 7 of WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer
Li, Z., Feng, M., Zhang, J., Wang, X., Xu, E., Wang, C., Lin, F., Yang, Z., Heng, Y., Guan, W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15139151
Additional file 3 of WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer
Li, Z., Feng, M., Zhang, J., Wang, X., Xu, E., Wang, C., Lin, F., Yang, Z., Yu, H., Guan, W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15139130
Additional file 2 of FBXW7 loss of function promotes esophageal squamous cell carcinoma progression via elevating MAP4 and ERK phosphorylation
Pan, Y., Liu, J., Gao, Y., Guo, Y., Wang, C., Liang, Z., Wu, M., Qian, Y., Li, Y., Shen, J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22624972
Additional file 6 of WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer
Li, Z., Feng, M., Zhang, J., Wang, X., Xu, E., Wang, C., Lin, F., Yang, Z., Heng, Y., Guan, W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15139145
Additional file 9 of WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer
Li, Z., Feng, M., Zhang, J., Wang, X., Xu, E., Wang, C., Lin, F., Yang, Z., Yu, H., Guan, W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15139160
Maternal methylosome protein 50 is essential for embryonic development in medaka Oryzias latipes
Duan, S., Yang, Q., Wu, F., Li, Z., Hong, W., Cao, M., Chen, X., Zhong, X., Zhou, Q., & Zhao, H. (2024) · Journal of Experimental Zoology Part A Ecological and Integrative Physiology · doi:10.1002/jez.2824
Zc3h4/Restrictor Exerts a Stranglehold on Unproductive TranscriptionPreprint
Estell, C., & West, S. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4829106
Initial Characterization of WDR5B Reveals a Role in the Proliferation of Retinal Pigment Epithelial Cells
Bailey, J., Ma, D., & Clegg, D. (2024) · Cells · doi:10.3390/cells13141189 · Cited by 1
“Many surfaces of the β -propeller structure have been shown to facilitate interactions including the top, bottom, sides, and central cavity [93,99].”
Background
Targeting Histone Readers: Non-bromodomain Readers
Huang, X., Chen, Y., Xiao, Q., Shang, X., & Liu, Y. (2024) · Royal Society of Chemistry eBooks · doi:10.1039/9781837674916-00440
Drug Discovery for Chromatin Readers, Writers, Erasers, Remodelers and Epitranscriptomic Targets
(2024) · Royal Society of Chemistry eBooks · doi:10.1039/9781837674916-part3
Immunoproteomic analyses identify broadly cross-reactive sporozoite immunogens of Eimeria maxima recognized by antisera from chickens infected with E. maxima, E. necatrix, E. tenella or E. acervulina
Gong, H., Deng, H., Song, F., Han, T., Wang, X., Feng, S., Chen, W., & Liu, L. (2025) · Veterinary Parasitology · doi:10.1016/j.vetpar.2025.110462
Inhibitors and degraders of epigenetic regulation in cancer
Gao, P., Kanıskan, H. Ü., & Jin, J. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-29808-0.00037-6
Additional file 2 of CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens
Vinceti, A., Karakoç, E., Pacini, C., Perron, U., Lucia, R. R. D., Garnett, M. J., & Iorio, F. (2021) · Figshare · doi:10.6084/m9.figshare.17037552
Additional file 6 of CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens
Vinceti, A., Karakoç, E., Pacini, C., Perron, U., Lucia, R. R. D., Garnett, M. J., & Iorio, F. (2021) · Figshare · doi:10.6084/m9.figshare.17037573
Additional file 1 of WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer
Li, Z., Feng, M., Zhang, J., Wang, X., Xu, E., Wang, C., Lin, F., Yang, Z., Yu, H., Guan, W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15139118
Additional file 5 of CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens
Vinceti, A., Karakoç, E., Pacini, C., Perron, U., Lucia, R. R. D., Garnett, M. J., & Iorio, F. (2021) · Figshare · doi:10.6084/m9.figshare.17037567
Additional file 7 of CoRe: a robustly benchmarked R package for identifying core-fitness genes in genome-wide pooled CRISPR-Cas9 screens
Vinceti, A., Karakoç, E., Pacini, C., Perron, U., Lucia, R. R. D., Garnett, M. J., & Iorio, F. (2021) · Figshare · doi:10.6084/m9.figshare.17037579
Additional file 2 of Central nervous system manifestations of LRBA deficiency: case report of two siblings and literature review
Mangodt, T. C., Vanden Driessche, K., Norga, K., Moes, N. D., de Bruyne, M., Haerynck, F., Bordon, V., Jansen, A. C., & Jonckheere, A. I. (2023) · Figshare · doi:10.6084/m9.figshare.23682345
Additional file 5 of WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer
Li, Z., Feng, M., Zhang, J., Wang, X., Xu, E., Wang, C., Lin, F., Yang, Z., Yu, H., Guan, W., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15139142
Additional file 2 of Pocket Crafter: a 3D generative modeling based workflow for the rapid generation of hit molecules in drug discovery
Shen, L., Fang, J., Liu, L., Yang, F., Jenkins, J. L., Kutchukian, P. S., & Wang, H. (2024) · Figshare · doi:10.6084/m9.figshare.26696520

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