The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Small‐Molecule‐Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging
Open accessAbstract
Androgen receptor (AR)‐dependent transcription is a major driver of prostate tumor cell proliferation. Consequently, it is the target of several antitumor chemotherapeutic agents, including the AR antagonist MDV3100/enzalutamide. Recent studies have shown that a single AR mutation (F876L) converts MDV3100 action from an antagonist to an agonist. Here we describe the generation of a novel class of selective androgen receptor degraders (SARDs) to address this resistance mechanism. Molecules containing hydrophobic degrons linked to small‐molecule AR ligands induce AR degradation, reduce expression of AR target genes and inhibit proliferation in androgen‐dependent prostate cancer cell lines. These results suggest that selective AR degradation may be an effective therapeutic prostate tumor strategy in the context of AR mutations that confer resistance to second‐generation AR antagonists.
Overview
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
Verification
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?
In the citing paper
“However, molecular chaperones Hsp70 and Hsp90 can also recruit the co-chaperone E3 ligase CHIP (C-terminus of Hsp70 interacting protein), which leads to ubiquitination and degradation of the chaperone-bound client proteins [56–59].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [57]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Huggins, C., & Hodges, C. V. (2002) · The Journal of Urology · doi:10.1016/s0022-5347(05)64820-3 · Cited by 3,856
HaloTag: A Novel Protein Labeling Technology for Cell Imaging and Protein Analysis
Los, G. V., Encell, L. P., McDougall, M. G., Hartzell, D. D., Karassina, N., Zimprich, C., Wood, M. G., Learish, R., Ohana, R. F., Urh, M., et al. (2008) · ACS Chemical Biology · doi:10.1021/cb800025k · Cited by 2,624
The development of androgen-independent prostate cancer.
Feldman, B. J., & Feldman, D. (2001) · Nature reviews. Cancer · doi:10.1038/35094009 · Cited by 2,326
Development of a second-generation antiandrogen for treatment of advanced prostate cancer.
Tran, C., Ouk, S., Clegg, N. J., Chen, Y., Watson, P. A., Arora, V., Wongvipat, J., Smith-Jones, P. M., Yoo, D., Kwon, A., et al. (2009) · Science · doi:10.1126/science.1168175 · Cited by 2,292
Androgen Receptor in Prostate Cancer
Heinlein, C. A., & Chang, C. (2004) · Endocrine Reviews · doi:10.1210/er.2002-0032 · Cited by 1,780
Strategies for silencing human disease using RNA interference
Kim, D. H., & Rossi, J. J. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2006 · Cited by 1,078
Attard, G., Reid, A. H. M., Yap, T. A., Raynaud, F., Dowsett, M., Settatree, S., Barrett, M., Parker, C., Martins, V., Folkerd, E., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.9749 · Cited by 903
Current prospects for RNA interference-based therapies
Davidson, B. L., & McCray, P. B. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2968 · Cited by 787
ARN-509: A Novel Antiandrogen for Prostate Cancer Treatment
Clegg, N. J., Wongvipat, J., Joseph, J. D., Tran, C., Ouk, S., Dilhas, A., Chen, Y., Grillot, K., Bischoff, E. D., Cai, L., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3948 · Cited by 663
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
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Huggins C., 1941, Cancer Res., 1, 293
Cited by
Sorted by citations
Items 201–216 of 216
BindingDB Entry 50007681: Achieving
BindingDB (2021) · UC San Diego · doi:10.7270/q2df6vk2
BindingDB (2025) · UC San Diego · doi:10.7270/q280579x
BindingDB (2026) · UC San Diego · doi:10.7270/q22j6hqn
BindingDB (2024) · UC San Diego · doi:10.7270/q29z99dk
BindingDB (2021) · UC San Diego · doi:10.7270/q27s7s54
BindingDB Entry 50015183: Hydrophobic Tagging-Induced Degradation of PDEδ in Colon Cancer Cells.
BindingDB (2023) · UC San Diego · doi:10.7270/q2pc368t
Wu, Z., Hu, L., Shi, T., Zhu, L., Yang, L., An, Q., Chen, D., Li, S., Li, R., & Meng, Q. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.119461
Metadata
- Authors
- Gustafson, J. L., Neklesa, T. K., Cox, C. S., Roth, A. G., Buckley, D. L., Tae, H. S., Sundberg, T. B., Stagg, D. B., Hines, J., McDonnell, D. P., Norris, J. D., & Crews, C. M.
- Affiliations
- Yale University (US)
- Duke University (US)
- Corresponding author
- Crews, Craig M.
- ORCID
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2015-06-17
- Volume
- 54
- Issue
- 33
- Pages
- 9659-9662
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- PMC
- PMC4547777
- OpenAlex
- W2117170436
- Cited by
- 206
- References
- 33
- Citations by year
- 2026: 20 · 2025: 23 · 2024: 17 · 2023: 22 · 2022: 22 · 2021: 15 · 2020: 23 · 2019: 18 · 2018: 17 · 2017: 16 · 2016: 11 · 2015: 1
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA139818)
- National Institute of General Medical Sciences (T32GM067543, F32GM10052101, F32GM100521)
- National Institute of Allergy and Infectious Diseases (R01AI084140)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Keywords
- androgen receptor, protein degradation, enzalutamide resistance, androgen receptor antagonists, prostate cancer, androgen receptor agonists, small-molecule ligands, drug resistance
- MeSH terms
- Antineoplastic Agents, Benzamides, Humans, Male, Nitriles, Phenylthiohydantoin, Prostate, Prostatic Neoplasms, Receptors, Androgen, Point Mutation, Drug Resistance, Neoplasm, Cell Line, Tumor, Cell Proliferation, Small Molecule Libraries, Hydrophobic and Hydrophilic Interactions, Androgen Receptor Antagonists, 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
