Discovery of ARD-2585 as an Exceptionally Potent and Orally Active PROTAC Degrader of Androgen Receptor for the Treatment of Advanced Prostate Cancer
dc.contributor.author | Xiang, W | |
dc.contributor.author | Zhao, L | |
dc.contributor.author | Han, X | |
dc.contributor.author | Qin, C | |
dc.contributor.author | Miao, B | |
dc.contributor.author | McEachern, D | |
dc.contributor.author | Wang, Y | |
dc.contributor.author | Metwally, H | |
dc.contributor.author | Kirchhoff, PD | |
dc.contributor.author | Wang, L | |
dc.contributor.author | Matvekas, A | |
dc.contributor.author | He, M | |
dc.contributor.author | Wen, B | |
dc.contributor.author | Sun, D | |
dc.contributor.author | Wang, S | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2024-01-23T21:14:51Z | |
dc.date.available | 2024-01-23T21:14:51Z | |
dc.date.issued | 2021-09-23 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.issn | 1520-4804 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/34473519 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/192128 | en |
dc.description.abstract | We report herein the discovery of exceptionally potent and orally bioavailable PROTAC AR degraders with ARD-2585 being the most promising compound. ARD-2585 achieves DC50values of ≤0.1 nM in the VCaP cell line with AR gene amplification and in the LNCaP cell line carrying an AR mutation. It potently inhibits cell growth with IC50values of 1.5 and 16.2 nM in the VCaP and LNCaP cell lines, respectively, and achieves excellent pharmacokinetics and 51% of oral bioavailability in mice. It is more efficacious than enzalutamide in inhibition of VCaP tumor growth and does not cause any sign of toxicity in mice. ARD-2585 is a promising AR degrader for extensive investigations for the treatment of advanced prostate cancer. | |
dc.format.medium | Print-Electronic | |
dc.language | eng | |
dc.publisher | American Chemical Society (ACS) | |
dc.subject | Adaptor Proteins, Signal Transducing | |
dc.subject | Androgen Receptor Antagonists | |
dc.subject | Animals | |
dc.subject | Antineoplastic Agents | |
dc.subject | Cell Line, Tumor | |
dc.subject | Drug Design | |
dc.subject | Humans | |
dc.subject | Male | |
dc.subject | Mice, SCID | |
dc.subject | Molecular Structure | |
dc.subject | Phthalimides | |
dc.subject | Piperidones | |
dc.subject | Prostatic Neoplasms, Castration-Resistant | |
dc.subject | Proteolysis | |
dc.subject | Receptors, Androgen | |
dc.subject | Structure-Activity Relationship | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.title | Discovery of ARD-2585 as an Exceptionally Potent and Orally Active PROTAC Degrader of Androgen Receptor for the Treatment of Advanced Prostate Cancer | |
dc.type | Article | |
dc.identifier.pmid | 34473519 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/192128/2/Discovery of ARD-2585 as an Exceptionally Potent and Orally Active PROTAC Degrader of Androgen Receptor for the Treatment of.pdf | |
dc.identifier.doi | 10.1021/acs.jmedchem.1c00900 | |
dc.identifier.doi | https://dx.doi.org/10.7302/22128 | |
dc.identifier.source | Journal of Medicinal Chemistry | |
dc.description.version | Published version | |
dc.date.updated | 2024-01-23T21:14:46Z | |
dc.identifier.orcid | 0000-0003-0904-220X | |
dc.identifier.orcid | 0000-0002-6406-2126 | |
dc.identifier.orcid | 0000-0002-8782-6950 | |
dc.identifier.volume | 64 | |
dc.identifier.issue | 18 | |
dc.identifier.startpage | 13487 | |
dc.identifier.endpage | 13509 | |
dc.identifier.name-orcid | Xiang, W | |
dc.identifier.name-orcid | Zhao, L | |
dc.identifier.name-orcid | Han, X; 0000-0003-0904-220X | |
dc.identifier.name-orcid | Qin, C | |
dc.identifier.name-orcid | Miao, B | |
dc.identifier.name-orcid | McEachern, D | |
dc.identifier.name-orcid | Wang, Y | |
dc.identifier.name-orcid | Metwally, H | |
dc.identifier.name-orcid | Kirchhoff, PD | |
dc.identifier.name-orcid | Wang, L | |
dc.identifier.name-orcid | Matvekas, A | |
dc.identifier.name-orcid | He, M | |
dc.identifier.name-orcid | Wen, B | |
dc.identifier.name-orcid | Sun, D; 0000-0002-6406-2126 | |
dc.identifier.name-orcid | Wang, S; 0000-0002-8782-6950 | |
dc.working.doi | 10.7302/22128 | en |
dc.owningcollname | Internal Medicine, Department of |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.