Selective estrogen receptor degraders with novel structural motifs induce regression in a tamoxifen-resistant breast cancer xenograft. Issue 3 (1st February 2019)

• Record Type: Journal Article
• Authors: Govek, Steven P.; Bonnefous, Celine; Julien, Jackaline D.; Nagasawa, Johnny Y.; Kahraman, Mehmet; Lai, Andiliy G.; Douglas, Karensa L.; Aparicio, Anna M.; Darimont, Beatrice D.; Grillot, Katherine L.; Joseph, James D.; Kaufman, Joshua A.; Lee, Kyoung-Jin; Lu, Nhin; Moon, Michael J.; Prudente, Rene Y.; Sensintaffar, John; Rix, Peter J.; Hager, Jeffrey H.; Smith, Nicholas D.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 3(2019)
• Page Start: 367
• Page End: 372
• Publication Date: 2019-02-01
• Subjects: Estrogen receptor -- Degrader -- SERD -- Breast cancer -- Tamoxifen-resistant; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.12.042
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Potent estrogen receptor ligands typically contain a phenolic hydrogen-bond donor. The indazole of the selective estrogen receptor degrader (SERD) ARN-810 is believed to mimic this. Disclosed herein is the discovery of ARN-810 analogs which lack this hydrogen-bond donor. These SERDs induced tumor regression in a tamoxifen-resistant breast cancer xenograft, demonstrating that the indazole NH is not necessary for robust ER-modulation and anti-tumor activity.