5AAU

Optimization of a novel binding motif to to (E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H- pyrido(3,4-b)indol-1-yl)phenyl)acrylic acid (AZD9496), a potent and orally bioavailable selective estrogen receptor downregulator and antagonist

Summary for 5AAU

• Entry DOI: 10.2210/pdb5aau/pdb
• Related: 5AAV
• Descriptor: ESTROGEN RECEPTOR, 3-(1-(4-Chlorophenyl)-3,4-dihydro-1H-pyrido(3,4-b)indol-2(9H)-yl)propanoic acid (3 entities in total)
• Functional Keywords: signaling protein, breast cancer, estrogen receptor downregulator, fulvestrant, azd9496, nuclear 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: 58052.83

Authors

Norman, R.A.,Bradbury, R.H.,de Almeida, C.,Andrews, D.M.,Ballard, P.,Buttar, D.,Callis, R.J.,Currie, G.S.,Curwen, J.O.,Davies, C.D.,de Savi, C.,Donald, C.S.,Feron, L.J.L.,Glossop, S.C.,Hayter, B.R.,Karoutchi, G.,Lamont, S.G.,MacFaul, P.,Moss, T.,Pearson, S.E.,Rabow, A.A.,Tonge, M.,Walker, G.E.,Weir, H.M.,Wilson, Z. (deposition date: 2015-07-28, release date: 2015-10-14, Last modification date: 2016-10-12)

• Primary citation: De Savi, C.,Bradbury, R.H.,Rabow, A.A.,Norman, R.A.,De Almeida, C.,Andrews, D.M.,Ballard, P.,Buttar, D.,Callis, R.,Currie, G.S.,Davies, C.,Donald, C.,Feron, L.,Hayter, B.R.,Hussain, S.,Karoutchi, G.,Lamont, S.,Macfaul, P.A.,Moss, T.A.,Pearson, S.,Tonge, M.,Walker, G.,Weir, H.,Wilson, Z.; Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-Fluoro-2-Methylpropyl)-3-Methyl-2, 3,4,9-Tetrahydro-1H-Pyrido[3,4-B]Indol-1-Yl)Phenyl)Acrylic Acid (Azd9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist.; J.Med.Chem., 58:8128-, 2015; PubMed: 26407012; DOI: 10.1021/ACS.JMEDCHEM.5B00984

Experimental method

X-RAY DIFFRACTION (1.9 Å)