5ACC

A Novel Oral Selective Estrogen Receptor Down-regulator, AZD9496, drives Tumour Growth Inhibition in Estrogen Receptor positive and ESR1 Mutant Models

Summary for 5ACC

• Entry DOI: 10.2210/pdb5acc/pdb
• Descriptor: ESTROGEN RECEPTOR, (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 (3 entities in total)
• Functional Keywords: signaling protein, serd, metastatic breast cancer, er mutation, esr1 mutation, combination therapy
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Isoform 1: Nucleus . Isoform 3: Nucleus. Nucleus: P03372
• Total number of polymer chains: 1
• Total formula weight: 28684.52

Authors

Norman, R.A.,Weir, H.M.,Bradbury, R.H.,Lawson, M.,Rabow, A.A.,Buttar, D.,Callis, R.J.,Curwen, J.O.,de Almeida, C.,Ballard, P.,Hulse, M.,Donald, C.S.,Feron, L.J.L.,Gingell, H.,Karoutchi, G.,MacFaul, P.,Moss, T.,Pearson, S.E.,Tonge, M.,Davies, G.,Walker, G.E.,Wilson, Z.,Rowlinson, R.,Powell, S.,Hemsley, P.,Linney, E.,Campbell, H.,Ghazoui, Z.,Sadler, C.,Richmond, G.,Pazolli, E.,Mazzola, A.M.,DCruz, C.,De Savi, C. (deposition date: 2015-08-15, release date: 2015-12-16)

• 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.J.,Currie, G.S.,Curwen, J.O.,Davies, C.D.,Donald, C.S.,Feron, L.J.L.,Gingell, H.,Glossop, S.C.,Hayter, B.R.,Hussain, S.,Karoutchi, G.,Lamont, S.G.,Macfaul, P.,Moss, T.A.,Pearson, S.E.,Tonge, M.,Walker, G.E.,Weir, H.M.,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 (1.88 Å)