Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer
dataset
posted on 2017-03-15, 15:20 authored by Heather E. Burks, Tinya Abrams, Christina A. Kirby, Jason Baird, Alexander Fekete, Lawrence G. Hamann, Sunkyu Kim, Franco Lombardo, Alice Loo, Danuta Lubicka, Kaitlin Macchi, Donald P. McDonnell, Yuji Mishina, John D. Norris, Jill Nunez, Chitra Saran, Yingchuan Sun, Noel M. Thomsen, Chunrong Wang, Jianling Wang, Stefan PeukertTetrahydroisoquinoline 40 has been identified as a potent ERα antagonist and
selective estrogen receptor degrader (SERD), exhibiting good oral
bioavailability, antitumor efficacy, and SERD activity in vivo. We
outline the discovery and
chemical optimization of the THIQ scaffold leading to THIQ 40 and showcase the racemization of the scaffold, pharmacokinetic studies
in preclinical species, and the in vivo efficacy of THIQ 40 in a MCF-7 human breast cancer xenograft model.
