Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.

Journal Article (Journal Article)

Tetrahydroisoquinoline 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.

Full Text

Duke Authors

Cited Authors

  • Burks, HE; Abrams, T; Kirby, CA; Baird, J; Fekete, A; Hamann, LG; Kim, S; Lombardo, F; Loo, A; Lubicka, D; Macchi, K; McDonnell, DP; Mishina, Y; Norris, JD; Nunez, J; Saran, C; Sun, Y; Thomsen, NM; Wang, C; Wang, J; Peukert, S

Published Date

  • April 13, 2017

Published In

Volume / Issue

  • 60 / 7

Start / End Page

  • 2790 - 2818

PubMed ID

  • 28296398

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

Digital Object Identifier (DOI)

  • 10.1021/acs.jmedchem.6b01468


  • eng

Conference Location

  • United States