5T97

ESTROGEN RECEPTOR ALPHA LIGAND BINDING DOMAIN IN COMPLEX WITH (2E)-3-(4-{(1R)-6-hydroxy-1-methyl-2-[4-(propan-2 -yl)phenyl]-1,2,3,4- tetrahydroisoquinolin-1-yl}phenyl)prop-2-enoic acid

Summary for 5T97

• Entry DOI: 10.2210/pdb5t97/pdb
• Related: 5T92
• Descriptor: Estrogen receptor, (2E)-3-(4-{(1R)-6-hydroxy-1-methyl-2-[4-(propan-2-yl)phenyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}phenyl)prop-2-enoic acid (3 entities in total)
• Functional Keywords: nuclear receptor, protein-ligand complex, hormone receptor
• Biological source: Homo sapiens (Human)
• Cellular location: Isoform 1: Nucleus . Isoform 3: Nucleus. Nucleus: P03372
• Total number of polymer chains: 2
• Total formula weight: 58650.82

Authors

Kirby, C.A.,Baird, J. (deposition date: 2016-09-09, release date: 2017-03-29, Last modification date: 2024-03-06)

Primary citation

Burks, H.E.,Abrams, T.,Kirby, C.A.,Baird, J.,Fekete, A.,Hamann, L.G.,Kim, S.,Lombardo, F.,Loo, A.,Lubicka, D.,Macchi, K.,McDonnell, D.P.,Mishina, Y.,Norris, J.D.,Nunez, J.,Saran, C.,Sun, Y.,Thomsen, N.M.,Wang, C.,Wang, J.,Peukert, S.
Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ER alpha + Breast Cancer.
J. Med. Chem., 60:2790-2818, 2017

PubMed Abstract: 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.

PubMed: 28296398
DOI: 10.1021/acs.jmedchem.6b01468

Experimental method

X-RAY DIFFRACTION (3 Å)