Fluorine in PDB 5acc: A Novel Oral Selective Estrogen Receptor Down-Regulator, AZD9496, Drives Tumour Growth Inhibition in Estrogen Receptor Positive and ESR1 Mutant Models

The structure of A Novel Oral Selective Estrogen Receptor Down-Regulator, AZD9496, Drives Tumour Growth Inhibition in Estrogen Receptor Positive and ESR1 Mutant Models, PDB code: 5acc was solved by R.A.Norman, H.M.Weir, R.H.Bradbury, M.Lawson, A.A.Rabow, D.Buttar, R.J.Callis, J.O.Curwen, C.De Almeida, P.Ballard, M.Hulse, C.S.Donald, L.J.L.Feron, H.Gingell, G.Karoutchi, P.Macfaul, T.Moss, S.E.Pearson, M.Tonge, G.Davies, G.E.Walker, Z.Wilson, R.Rowlinson, S.Powell, P.Hemsley, E.Linney, H.Campbell, Z.Ghazoui, C.Sadler, G.Richmond, E.Pazolli, A.M.Mazzola, C.Dcruz, C.De Savi, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	50.11 / 1.88
Space group	P 65 2 2
Cell size a, b, c (Å), α, β, γ (°)	57.860, 57.860, 274.040, 90.00, 90.00, 120.00
R / Rfree (%)	21.685 / 26.628

The binding sites of Fluorine atom in the A Novel Oral Selective Estrogen Receptor Down-Regulator, AZD9496, Drives Tumour Growth Inhibition in Estrogen Receptor Positive and ESR1 Mutant Models (pdb code 5acc). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the A Novel Oral Selective Estrogen Receptor Down-Regulator, AZD9496, Drives Tumour Growth Inhibition in Estrogen Receptor Positive and ESR1 Mutant Models, PDB code: 5acc:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the A Novel Oral Selective Estrogen Receptor Down-Regulator, AZD9496, Drives Tumour Growth Inhibition in Estrogen Receptor Positive and ESR1 Mutant Models


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of A Novel Oral Selective Estrogen Receptor Down-Regulator, AZD9496, Drives Tumour Growth Inhibition in Estrogen Receptor Positive and ESR1 Mutant Models within 5.0Å range: probe atom residue distance (Å) B Occ A:F1546 b:16.6 occ:1.00 F22 A:KE91546 0.0 16.6 1.0 C19 A:KE91546 1.4 16.6 1.0 C21 A:KE91546 2.3 16.3 1.0 C20 A:KE91546 2.3 17.2 1.0 C18 A:KE91546 2.4 16.1 1.0 N17 A:KE91546 2.9 15.9 1.0 C2 A:KE91546 3.2 15.5 1.0 CA A:GLY521 3.3 29.3 1.0 CE A:MET388 3.6 23.2 1.0 CD1 A:ILE424 3.7 29.4 1.0 CG2 A:ILE424 3.8 25.6 1.0 C1 A:KE91546 4.2 15.4 1.0 C A:GLY521 4.2 31.8 1.0 C4 A:KE91546 4.3 15.5 1.0 CD2 A:LEU384 4.3 24.0 1.0 O A:GLY521 4.4 34.0 1.0 N A:GLY521 4.4 27.5 1.0 C15 A:KE91546 4.4 16.4 1.0 CG1 A:ILE424 4.6 28.0 1.0 CB A:ILE424 4.7 26.5 1.0 CD1 A:LEU384 4.7 23.6 1.0 C23 A:KE91546 4.8 17.4 1.0

Fluorine binding site 2 out of 3 in the A Novel Oral Selective Estrogen Receptor Down-Regulator, AZD9496, Drives Tumour Growth Inhibition in Estrogen Receptor Positive and ESR1 Mutant Models


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of A Novel Oral Selective Estrogen Receptor Down-Regulator, AZD9496, Drives Tumour Growth Inhibition in Estrogen Receptor Positive and ESR1 Mutant Models within 5.0Å range: probe atom residue distance (Å) B Occ A:F1546 b:17.8 occ:1.00 F29 A:KE91546 0.0 17.8 1.0 C28 A:KE91546 1.3 18.1 1.0 C27 A:KE91546 2.3 19.5 1.0 C23 A:KE91546 2.3 17.4 1.0 C15 A:KE91546 2.9 16.4 1.0 CB A:LEU346 3.2 30.8 1.0 C18 A:KE91546 3.5 16.1 1.0 SD A:MET343 3.5 49.0 1.0 C24 A:KE91546 3.6 17.8 1.0 C26 A:KE91546 3.6 20.3 1.0 N17 A:KE91546 3.7 15.9 1.0 C A:LEU346 4.0 31.6 1.0 N A:THR347 4.1 33.0 1.0 C25 A:KE91546 4.1 18.9 1.0 C14 A:KE91546 4.1 15.9 1.0 OG1 A:THR347 4.1 35.6 1.0 CD1 A:LEU346 4.1 30.6 1.0 CE A:MET421 4.2 36.3 1.0 CE A:MET343 4.2 47.4 1.0 CA A:LEU346 4.2 31.6 1.0 O A:MET343 4.3 38.0 1.0 CG A:LEU346 4.3 31.1 1.0 O A:LEU346 4.4 29.9 1.0 N12 A:KE91546 4.5 15.4 1.0 C19 A:KE91546 4.5 16.6 1.0 CA A:THR347 4.6 34.3 1.0 F35 A:KE91546 4.7 18.1 1.0 C21 A:KE91546 4.7 16.3 1.0 C30 A:KE91546 4.8 23.3 1.0 C20 A:KE91546 4.8 17.2 1.0 CG A:MET343 4.8 47.0 1.0 CA A:MET343 4.9 42.0 1.0

Fluorine binding site 3 out of 3 in the A Novel Oral Selective Estrogen Receptor Down-Regulator, AZD9496, Drives Tumour Growth Inhibition in Estrogen Receptor Positive and ESR1 Mutant Models


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of A Novel Oral Selective Estrogen Receptor Down-Regulator, AZD9496, Drives Tumour Growth Inhibition in Estrogen Receptor Positive and ESR1 Mutant Models within 5.0Å range: probe atom residue distance (Å) B Occ A:F1546 b:18.1 occ:1.00 F35 A:KE91546 0.0 18.1 1.0 C24 A:KE91546 1.3 17.8 1.0 C25 A:KE91546 2.3 18.9 1.0 C23 A:KE91546 2.3 17.4 1.0 C14 A:KE91546 2.7 15.9 1.0 C15 A:KE91546 2.8 16.4 1.0 C5 A:KE91546 3.2 15.3 1.0 N17 A:KE91546 3.2 15.9 1.0 N12 A:KE91546 3.2 15.4 1.0 CD1 A:LEU384 3.4 23.6 1.0 C28 A:KE91546 3.6 18.1 1.0 C26 A:KE91546 3.6 20.3 1.0 CB A:ALA350 3.7 31.7 1.0 C21 A:KE91546 3.7 16.3 1.0 C4 A:KE91546 3.7 15.5 1.0 C6 A:KE91546 3.8 15.1 1.0 C11 A:KE91546 3.9 15.3 1.0 CD1 A:LEU387 3.9 28.2 1.0 C27 A:KE91546 4.1 19.5 1.0 C2 A:KE91546 4.1 15.5 1.0 CZ3 A:TRP383 4.2 30.4 1.0 C18 A:KE91546 4.3 16.1 1.0 C19 A:KE91546 4.5 16.6 1.0 CH2 A:TRP383 4.6 31.1 1.0 F29 A:KE91546 4.7 17.8 1.0 C30 A:KE91546 4.8 23.3 1.0 CG A:LEU384 4.8 23.5 1.0 O A:LEU346 4.8 29.9 1.0 C7 A:KE91546 4.9 15.3 1.0 C10 A:KE91546 4.9 15.8 1.0 CA A:ALA350 4.9 32.5 1.0

C.De Savi, R.H.Bradbury, A.A.Rabow, R.A.Norman, C.De Almeida, D.M.Andrews, P.Ballard, D.Buttar, R.J.Callis, G.S.Currie, J.O.Curwen, C.D.Davies, C.S.Donald, L.J.L.Feron, H.Gingell, S.C.Glossop, B.R.Hayter, S.Hussain, G.Karoutchi, S.G.Lamont, P.Macfaul, T.A.Moss, S.E.Pearson, M.Tonge, G.E.Walker, H.M.Weir, Z.Wilson. 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. V. 58 8128 2015.
ISSN: ISSN 0022-2623
PubMed: 26407012
DOI: 10.1021/ACS.JMEDCHEM.5B00984