Seragon Pharmaceuticals, Inc., 12780 El Camino Real, Suite 302, San Diego, CA 92130, United States.
Seragon Pharmaceuticals, Inc., 12780 El Camino Real, Suite 302, San Diego, CA 92130, United States.
Bioorg Med Chem Lett. 2019 Feb 1;29(3):367-372. doi: 10.1016/j.bmcl.2018.12.042. Epub 2018 Dec 19.
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.
强效雌激素受体配体通常含有酚类氢键供体。选择性雌激素受体降解剂（SERD）ARN-810 的吲唑被认为模拟了这种作用。本文披露了缺乏这种氢键供体的 ARN-810 类似物的发现。这些 SERD 在他莫昔芬耐药乳腺癌异种移植模型中诱导肿瘤消退，表明吲唑 NH 对于强大的 ER 调节和抗肿瘤活性不是必需的。
