Chlorine in PDB 6b3w: Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One

The structure of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One, PDB code: 6b3w was solved by K.S.Gajiwala, A.Brooun, W.Liu, Y.Deng, A.E.Stewart, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	147.34 / 3.05
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	70.778, 115.178, 150.967, 90.00, 102.58, 90.00
R / Rfree (%)	n/a / n/a

The structure of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One also contains other interesting chemical elements:

Zinc

(Zn)

14 atoms

The binding sites of Chlorine atom in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One (pdb code 6b3w). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 4 binding sites of Chlorine where determined in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One, PDB code: 6b3w:
Jump to Chlorine binding site number: 1; 2; 3; 4;

Chlorine binding site 1 out of 4 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl708 b:57.4 occ:1.00 CL22 A:CJG708 0.0 57.4 1.0 C4 A:CJG708 1.7 55.7 1.0 C3 A:CJG708 2.6 55.3 1.0 C5 A:CJG708 2.7 57.0 1.0 C10 A:CJG708 3.2 56.8 1.0 CD1 A:TYR558 3.7 47.9 1.0 CB A:TYR558 3.8 51.3 1.0 C2 A:CJG708 4.0 53.5 1.0 SG A:CYS560 4.0 56.5 1.0 C6 A:CJG708 4.1 56.7 1.0 O A:TYR558 4.1 55.6 1.0 CG A:TYR558 4.2 48.7 1.0 C9 A:CJG708 4.5 54.9 1.0 C1 A:CJG708 4.5 54.4 1.0 CB A:CYS560 4.6 55.6 1.0 CA A:TYR558 4.7 54.2 1.0 CE1 A:TYR558 4.7 47.9 1.0 CE2 A:TYR111 4.8 44.1 1.0 C A:TYR558 4.9 55.3 1.0

Chlorine binding site 2 out of 4 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl708 b:55.3 occ:1.00 CL30 A:CJG708 0.0 55.3 1.0 C1 A:CJG708 1.7 54.4 1.0 C2 A:CJG708 2.7 53.5 1.0 C6 A:CJG708 2.8 56.7 1.0 O21 A:CJG708 2.9 60.6 1.0 C23 A:CJG708 3.1 50.1 1.0 C7 A:CJG708 3.2 57.3 1.0 C24 A:CJG708 3.6 48.8 1.0 C27 A:CJG708 3.8 49.1 1.0 CB A:TYR111 3.9 43.3 1.0 C3 A:CJG708 4.0 55.3 1.0 C29 A:CJG708 4.0 47.3 1.0 CG2 A:THR575 4.0 39.0 1.0 C5 A:CJG708 4.1 57.0 1.0 CD2 A:TYR111 4.2 45.7 1.0 O A:THR575 4.3 37.8 1.0 CG A:TYR111 4.4 45.2 1.0 C28 A:CJG708 4.5 47.6 1.0 CE2 A:PHE562 4.5 47.5 1.0 N25 A:CJG708 4.5 47.6 1.0 N8 A:CJG708 4.6 55.0 1.0 O26 A:CJG708 4.6 49.2 1.0 C4 A:CJG708 4.6 55.7 1.0 CD2 A:PHE562 4.7 48.7 1.0 N A:TYR111 4.8 44.7 1.0 C20 A:CJG708 4.8 43.3 1.0 CA A:TYR111 4.9 43.7 1.0 CA A:THR575 5.0 38.1 1.0

Chlorine binding site 3 out of 4 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 3 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl708 b:58.0 occ:1.00 CL22 B:CJG708 0.0 58.0 1.0 C4 B:CJG708 1.7 55.3 1.0 C3 B:CJG708 2.7 54.5 1.0 C5 B:CJG708 2.8 55.0 1.0 C10 B:CJG708 3.1 54.3 1.0 SG B:CYS560 3.9 59.7 1.0 CB B:TYR558 4.0 54.1 1.0 O B:TYR558 4.0 55.6 1.0 CD1 B:TYR558 4.0 50.0 1.0 C2 B:CJG708 4.0 53.8 1.0 C6 B:CJG708 4.1 54.7 1.0 CG B:TYR558 4.4 51.7 1.0 C9 B:CJG708 4.4 52.8 1.0 C1 B:CJG708 4.6 54.5 1.0 CB B:CYS560 4.6 57.5 1.0 CE2 B:TYR111 4.7 43.8 1.0 CA B:TYR558 4.8 56.1 1.0 C B:TYR558 4.8 56.7 1.0 CG2 B:ILE109 4.9 40.6 1.0

Chlorine binding site 4 out of 4 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 4 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-7-(3,5-Dimethyl-1, 2-Oxazol-4-Yl)-2-[(4,6-Dimethyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl708 b:57.1 occ:1.00 CL30 B:CJG708 0.0 57.1 1.0 C1 B:CJG708 1.7 54.5 1.0 C2 B:CJG708 2.7 53.8 1.0 C6 B:CJG708 2.8 54.7 1.0 O21 B:CJG708 2.9 53.7 1.0 C23 B:CJG708 3.1 52.3 1.0 C7 B:CJG708 3.2 54.0 1.0 C24 B:CJG708 3.6 52.4 1.0 C27 B:CJG708 3.9 51.1 1.0 C29 B:CJG708 3.9 52.0 1.0 CB B:TYR111 3.9 42.5 1.0 C3 B:CJG708 4.1 54.5 1.0 C5 B:CJG708 4.1 55.0 1.0 CG2 B:THR575 4.2 37.6 1.0 CD2 B:TYR111 4.2 45.0 1.0 CE2 B:PHE562 4.3 46.5 1.0 N25 B:CJG708 4.5 52.4 1.0 O B:THR575 4.5 39.1 1.0 CG B:TYR111 4.5 44.6 1.0 N8 B:CJG708 4.6 53.2 1.0 C28 B:CJG708 4.6 51.1 1.0 O26 B:CJG708 4.6 50.5 1.0 C4 B:CJG708 4.6 55.3 1.0 CD2 B:PHE562 4.6 47.4 1.0 C20 B:CJG708 4.9 47.3 1.0 CA B:TYR111 4.9 41.2 1.0 N B:TYR111 4.9 40.7 1.0

P.P.Kung, P.Bingham, A.Brooun, M.Collins, Y.L.Deng, D.Dinh, C.Fan, K.S.Gajiwala, R.Grantner, H.J.Gukasyan, W.Hu, B.Huang, R.Kania, S.E.Kephart, C.Krivacic, R.A.Kumpf, P.Khamphavong, M.Kraus, W.Liu, K.A.Maegley, L.Nguyen, S.Ren, D.Richter, R.A.Rollins, N.Sach, S.Sharma, J.Sherrill, J.Spangler, A.E.Stewart, S.Sutton, S.Uryu, D.Verhelle, H.Wang, S.Wang, M.Wythes, S.Xin, S.Yamazaki, H.Zhu, J.Zhu, L.Zehnder, M.Edwards. Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(Methoxy(Oxetan-3-Yl)Methyl) -2-((4-Methoxy-6-Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl)-3,4-Dihydroisoquinolin-1(2H)-One (Pf-06821497). J. Med. Chem. V. 61 650 2018.
ISSN: ISSN 1520-4804
PubMed: 29211475
DOI: 10.1021/ACS.JMEDCHEM.7B01375