Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.

Journal Article (Journal Article)

In breast cancer, estrogen receptor alpha (ERα) positive cancer accounts for approximately 74% of all diagnoses, and in these settings, it is a primary driver of cell proliferation. Treatment of ERα positive breast cancer has long relied on endocrine therapies such as selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders (SERDs). The steroid-based anti-estrogen fulvestrant (5), the only approved SERD, is effective in patients who have not previously been treated with endocrine therapy as well as in patients who have progressed after receiving other endocrine therapies. Its efficacy, however, may be limited due to its poor physicochemical properties. We describe the design and synthesis of a series of potent benzothiophene-containing compounds that exhibit oral bioavailability and preclinical activity as SERDs. This article culminates in the identification of LSZ102 (10), a compound in clinical development for the treatment of ERα positive breast cancer.

Full Text

Duke Authors

Cited Authors

  • Tria, GS; Abrams, T; Baird, J; Burks, HE; Firestone, B; Gaither, LA; Hamann, LG; He, G; Kirby, CA; Kim, S; Lombardo, F; Macchi, KJ; McDonnell, DP; Mishina, Y; Norris, JD; Nunez, J; Springer, C; Sun, Y; Thomsen, NM; Wang, C; Wang, J; Yu, B; Tiong-Yip, C-L; Peukert, S

Published Date

  • April 12, 2018

Published In

Volume / Issue

  • 61 / 7

Start / End Page

  • 2837 - 2864

PubMed ID

  • 29562737

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

Digital Object Identifier (DOI)

  • 10.1021/acs.jmedchem.7b01682


  • eng

Conference Location

  • United States