Selective estrogen receptor degraders with novel structural motifs induce regression in a tamoxifen-resistant breast cancer xenograft

Abstract Potent estrogen receptorligands typically contain a phenolic hydrogen-bond donor. The indazoleof the selective estrogen receptordegrader ( SERD) ARN-810 is believed to mimic this. Disclosed herein is the discovery of ARN-810 analogs which lack this hydrogen-bond donor. These SERDsinduced tumor regression in a tamoxifen-resistant breast cancer xenograft, demonstrating that the indazoleNH is not necessary for robust ER-modulation and anti-tumor activity.