Fluorine in PDB 6ucs: Discovery and Structure-Based Optimization of Potent and Selective WDR5 Inhibitors Containing A Dihydroisoquinolinone Bicyclic Core

The structure of Discovery and Structure-Based Optimization of Potent and Selective WDR5 Inhibitors Containing A Dihydroisoquinolinone Bicyclic Core, PDB code: 6ucs was solved by B.Zhao, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	28.24 / 1.85
Space group	P 1
Cell size a, b, c (Å), α, β, γ (°)	46.566, 47.099, 68.984, 89.06, 89.82, 74.18
R / Rfree (%)	16.7 / 19.4

The binding sites of Fluorine atom in the Discovery and Structure-Based Optimization of Potent and Selective WDR5 Inhibitors Containing A Dihydroisoquinolinone Bicyclic Core (pdb code 6ucs). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the Discovery and Structure-Based Optimization of Potent and Selective WDR5 Inhibitors Containing A Dihydroisoquinolinone Bicyclic Core, PDB code: 6ucs:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in the Discovery and Structure-Based Optimization of Potent and Selective WDR5 Inhibitors Containing A Dihydroisoquinolinone Bicyclic Core


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Discovery and Structure-Based Optimization of Potent and Selective WDR5 Inhibitors Containing A Dihydroisoquinolinone Bicyclic Core within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:22.8 occ:1.00 F01 A:Q41401 0.0 22.8 1.0 C16 A:Q41401 1.4 19.4 1.0 C22 A:Q41401 2.4 18.6 1.0 C17 A:Q41401 2.4 18.4 1.0 CA A:ALA65 3.2 14.3 1.0 CB A:ALA65 3.4 11.1 1.0 O A:ILE90 3.5 12.7 1.0 CA A:GLY89 3.6 14.7 1.0 C21 A:Q41401 3.6 18.4 1.0 C18 A:Q41401 3.6 16.3 1.0 C A:GLY89 3.6 15.3 1.0 N A:ILE90 3.6 14.7 1.0 N A:ALA65 3.7 11.6 1.0 C A:ILE90 3.9 13.9 1.0 C20 A:Q41401 4.1 16.9 1.0 C A:SER64 4.3 11.4 1.0 O A:SER64 4.3 14.5 1.0 O A:GLY89 4.3 16.2 1.0 OD2 A:ASP107 4.3 22.5 1.0 CA A:ILE90 4.4 15.6 1.0 C A:ALA65 4.4 15.4 1.0 N A:SER91 4.5 13.3 0.5 N A:SER91 4.5 13.4 0.5 O A:ALA65 4.7 14.2 1.0 N A:GLY89 4.7 12.0 1.0 CA A:SER91 4.8 12.9 0.5 CA A:SER91 4.8 12.9 0.5 CG A:ASP107 4.9 19.4 1.0 C19 A:Q41401 4.9 16.7 1.0 OG A:SER91 4.9 12.0 0.5

Fluorine binding site 2 out of 2 in the Discovery and Structure-Based Optimization of Potent and Selective WDR5 Inhibitors Containing A Dihydroisoquinolinone Bicyclic Core


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Discovery and Structure-Based Optimization of Potent and Selective WDR5 Inhibitors Containing A Dihydroisoquinolinone Bicyclic Core within 5.0Å range: probe atom residue distance (Å) B Occ B:F401 b:23.5 occ:1.00 F01 B:Q41401 0.0 23.5 1.0 C16 B:Q41401 1.4 21.9 1.0 C17 B:Q41401 2.4 20.2 1.0 C22 B:Q41401 2.4 20.6 1.0 CA B:ALA65 3.2 17.1 1.0 CB B:ALA65 3.5 16.4 1.0 CA B:GLY89 3.5 16.9 1.0 O B:ILE90 3.5 13.9 1.0 C B:GLY89 3.6 18.9 1.0 N B:ILE90 3.6 17.0 1.0 C21 B:Q41401 3.6 19.9 1.0 C18 B:Q41401 3.6 18.0 1.0 N B:ALA65 3.8 14.7 1.0 C B:ILE90 3.9 15.3 1.0 C20 B:Q41401 4.1 17.1 1.0 OD2 B:ASP107 4.1 27.1 1.0 O B:GLY89 4.2 18.2 1.0 O B:SER64 4.3 16.7 1.0 C B:SER64 4.3 15.8 1.0 CA B:ILE90 4.4 15.8 1.0 C B:ALA65 4.4 19.7 1.0 N B:SER91 4.5 11.7 1.0 N B:GLY89 4.6 17.4 1.0 O B:ALA65 4.7 17.8 1.0 CG B:ASP107 4.7 24.4 1.0 CA B:SER91 4.8 11.4 1.0 C19 B:Q41401 4.9 15.5 1.0 O B:HOH550 4.9 50.8 1.0 OD1 B:ASP107 4.9 22.7 1.0 O B:HOH714 5.0 34.5 1.0 O B:HOH636 5.0 35.3 1.0

J.Tian, K.Teuscher, E.R.Aho, J.R.Alvarado, J.J.Mills, K.M.Meyers, R.D.Gogliotti, C.Han, J.D.Macdonald, J.Sai, J.G.Shaw, J.L.Sensintaffar, B.Zhao, T.A.Rietz, L.R.Thomas, W.G.Payne, W.J.Moore, G.M.Stott, J.Kondo, M.Inoue, R.Coffey, W.P.Tansey, S.Stauffer, T.Lee, S.W.Fesik. Discovery and Structure-Based Optimization of Potent and Selective Wd Repeat Domain 5 (WDR5) Inhibitors Containing A Dihydroisoquinolinone Bicyclic Core. J.Med.Chem. 2019.
ISSN: ISSN 0022-2623
PubMed: 31858797
DOI: 10.1021/ACS.JMEDCHEM.9B01608