414861-48-6Relevant articles and documents
Discovery of LSZ102, a potent, orally bioavailable selective estrogen receptor degrader (SERD) for the treatment of estrogen receptor positive breast cancer
Tria, George S.,Abrams, Tinya,Baird, Jason,Burks, Heather E.,Firestone, Brant,Gaither, L. Alex,Hamann, Lawrence G.,He, Guo,Kirby, Christina A.,Kim, Sunkyu,Lombardo, Franco,Macchi, Kaitlin J.,McDonnell, Donald P.,Mishina, Yuji,Norris, John D.,Nunez, Jill,Springer, Clayton,Sun, Yingchuan,Thomsen, Noel M.,Wang, Chunrong,Wang, Jianling,Yu, Bing,Tiong-Yip, Choi-Lai,Peukert, Stefan
supporting information, p. 2837 - 2864 (2018/04/23)
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.
Toward selective ERβ agonists for central nervous system disorders: Synthesis and characterization of aryl benzthiophenes
Schopfer, Ulrich,Schoeffter, Philippe,Bischoff, Serge F.,Nozulak, Joachim,Feuerbach, Dominik,Floersheim, Philipp
, p. 1399 - 1401 (2007/10/03)
In an effort to identify selective for the estrogen receptor subtype ERβ, a series of aryl benzthiophenes was synthesized. In a radioligand binding assay and reporter gene assat in HeLa and SH-SY5Y cells, compound were characterized as ERβ-selective agonists. By targeting ERβ in the brain, these compounds could lead to drugs able to separate the beneficial effects of estrogens on mood, learning, and memory from side effects such as the stimulation of edometrial and breast cancer.
