Discovery of ERD-3111 as a Potent and Orally Efficacious Estrogen Receptor PROTAC Degrader with Strong Antitumor Activity.
dc.contributor.author | Chen, Zhixiang | |
dc.contributor.author | Hu, Biao | |
dc.contributor.author | Rej, Rohan Kalyan | |
dc.contributor.author | Wu, Dimin | |
dc.contributor.author | Acharyya, Ranjan Kumar | |
dc.contributor.author | Wang, Mingliang | |
dc.contributor.author | Xu, Tianfeng | |
dc.contributor.author | Lu, Jianfeng | |
dc.contributor.author | Metwally, Hoda | |
dc.contributor.author | Wang, Yu | |
dc.contributor.author | McEachern, Donna | |
dc.contributor.author | Bai, Longchuan | |
dc.contributor.author | Gersch, Christina L | |
dc.contributor.author | Wang, Meilin | |
dc.contributor.author | Zhang, Wenjing | |
dc.contributor.author | Li, Qiuxia | |
dc.contributor.author | Wen, Bo | |
dc.contributor.author | Sun, Duxin | |
dc.contributor.author | Rae, James M | |
dc.contributor.author | Wang, Shaomeng | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-09-13T13:04:50Z | |
dc.date.available | 2023-09-13T13:04:50Z | |
dc.date.issued | 2023-08-30 | |
dc.identifier.issn | 0022-2623 | |
dc.identifier.issn | 1520-4804 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/37647546 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/177662 | en |
dc.description.abstract | Estrogen receptor α (ERα) is a prime target for the treatment of ER-positive (ER+) breast cancer. Despite the development of several effective therapies targeting ERα signaling, clinical resistance remains a major challenge. In this study, we report the discovery of a new class of potent and orally bioavailable ERα degraders using the PROTAC technology, with ERD-3111 being the most promising compound. ERD-3111 exhibits potent in vitro degradation activity against ERα and demonstrates high oral bioavailability in mice, rats, and dogs. Oral administration of ERD-3111 effectively reduces the levels of wild-type and mutated ERα proteins in tumor tissues. ERD-3111 achieves tumor regression or complete tumor growth inhibition in the parental MCF-7 xenograft model with wild-type ER and two clinically relevant ESR1 mutated models in mice. ERD-3111 is a promising ERα degrader for further extensive evaluations for the treatment of ER+ breast cancer. | |
dc.format.medium | Print-Electronic | |
dc.language | eng | |
dc.publisher | American Chemical Society (ACS) | |
dc.title | Discovery of ERD-3111 as a Potent and Orally Efficacious Estrogen Receptor PROTAC Degrader with Strong Antitumor Activity. | |
dc.type | Article | |
dc.identifier.pmid | 37647546 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/177662/2/Discovery of ERD-3111.pdf | |
dc.identifier.doi | 10.1021/acs.jmedchem.3c01186 | |
dc.identifier.doi | https://dx.doi.org/10.7302/8119 | |
dc.identifier.source | J Med Chem | |
dc.description.version | Published online | |
dc.date.updated | 2023-09-13T13:04:46Z | |
dc.identifier.orcid | 0000-0002-4691-6490 | |
dc.identifier.orcid | 0000-0003-0904-9137 | |
dc.identifier.orcid | 0000-0001-8996-4065 | |
dc.identifier.orcid | 0000-0002-6406-2126 | |
dc.identifier.orcid | 0000-0002-8782-6950 | |
dc.identifier.name-orcid | Chen, Zhixiang | |
dc.identifier.name-orcid | Hu, Biao; 0000-0002-4691-6490 | |
dc.identifier.name-orcid | Rej, Rohan Kalyan; 0000-0003-0904-9137 | |
dc.identifier.name-orcid | Wu, Dimin | |
dc.identifier.name-orcid | Acharyya, Ranjan Kumar | |
dc.identifier.name-orcid | Wang, Mingliang | |
dc.identifier.name-orcid | Xu, Tianfeng; 0000-0001-8996-4065 | |
dc.identifier.name-orcid | Lu, Jianfeng | |
dc.identifier.name-orcid | Metwally, Hoda | |
dc.identifier.name-orcid | Wang, Yu | |
dc.identifier.name-orcid | McEachern, Donna | |
dc.identifier.name-orcid | Bai, Longchuan | |
dc.identifier.name-orcid | Gersch, Christina L | |
dc.identifier.name-orcid | Wang, Meilin | |
dc.identifier.name-orcid | Zhang, Wenjing | |
dc.identifier.name-orcid | Li, Qiuxia | |
dc.identifier.name-orcid | Wen, Bo | |
dc.identifier.name-orcid | Sun, Duxin; 0000-0002-6406-2126 | |
dc.identifier.name-orcid | Rae, James M | |
dc.identifier.name-orcid | Wang, Shaomeng; 0000-0002-8782-6950 | |
dc.working.doi | 10.7302/8119 | en |
dc.owningcollname | Internal Medicine, Department of |
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