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

Autor:	Burks Heather Elizabeth, Noel Marie-France Thomsen, Alexander Fekete, Alice Loo, Christina A. Kirby, Lawrence G. Hamann, Yingchuan Sun, Chunrong Wang, Jianling Wang, Chitra Saran, Danuta Lubicka, Donald P. McDonnell, Yuji Mishina, Franco Lombardo, Jason Baird, Tinya Abrams, Kaitlin J. Macchi, Stefan Peukert, Jill Nunez, John D. Norris, Sunkyu Kim
Rok vydání:	2017
Předmět:	Estrogen receptor Administration Oral Antineoplastic Agents Breast Neoplasms Pharmacology 01 natural sciences 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Dogs In vivo Tetrahydroisoquinolines Drug Discovery medicine Animals Humans Breast 010405 organic chemistry Tetrahydroisoquinoline Drug discovery Estrogen Receptor alpha Cancer medicine.disease 0104 chemical sciences Mice Inbred C57BL Molecular Docking Simulation chemistry Acrylates Hormone receptor 030220 oncology & carcinogenesis THIQ Proteolysis MCF-7 Cells Molecular Medicine Female Estrogen receptor alpha medicine.drug
Zdroj:	Journal of medicinal chemistry. 60(7)
ISSN:	1520-4804
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd2485b0e5060d74e1c48169d18047b1 https://pubmed.ncbi.nlm.nih.gov/28296398 Zobrazit plný text záznamu