Fluorine in PDB 7u9y: WDR5 Bound to 2-(3,5-Dimethoxybenzyl)-7-((2-Methyl-1H-Imidazol-1-Yl) Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-3,4- Dihydroisoquinolin-1(2H)-One

The structure of WDR5 Bound to 2-(3,5-Dimethoxybenzyl)-7-((2-Methyl-1H-Imidazol-1-Yl) Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-3,4- Dihydroisoquinolin-1(2H)-One, PDB code: 7u9y was solved by T.Rietz, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	29.55 / 1.90
Space group	P 21 21 2
Cell size a, b, c (Å), α, β, γ (°)	81.259, 86.122, 41.094, 90, 90, 90
R / Rfree (%)	14.8 / 18.9

The binding sites of Fluorine atom in the WDR5 Bound to 2-(3,5-Dimethoxybenzyl)-7-((2-Methyl-1H-Imidazol-1-Yl) Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-3,4- Dihydroisoquinolin-1(2H)-One (pdb code 7u9y). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the WDR5 Bound to 2-(3,5-Dimethoxybenzyl)-7-((2-Methyl-1H-Imidazol-1-Yl) Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-3,4- Dihydroisoquinolin-1(2H)-One, PDB code: 7u9y:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the WDR5 Bound to 2-(3,5-Dimethoxybenzyl)-7-((2-Methyl-1H-Imidazol-1-Yl) Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-3,4- Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of WDR5 Bound to 2-(3,5-Dimethoxybenzyl)-7-((2-Methyl-1H-Imidazol-1-Yl) Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-3,4- Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:F402 b:20.1 occ:1.00 F1 A:M4U402 0.0 20.1 1.0 C20 A:M4U402 1.3 21.1 1.0 F2 A:M4U402 2.1 21.1 1.0 F3 A:M4U402 2.1 19.6 1.0 C14 A:M4U402 2.3 16.7 1.0 N3 A:M4U402 3.2 16.2 1.0 CD2 A:LEU321 3.2 13.2 1.0 C10 A:M4U402 3.3 15.0 1.0 O A:VAL48 3.5 14.7 1.0 CB A:ALA47 3.5 18.6 1.0 CA A:SER49 3.7 9.8 1.0 C1 A:M4U402 3.7 10.8 1.0 CB A:SER49 3.8 12.4 1.0 C A:VAL48 3.9 14.3 1.0 C6 A:M4U402 4.0 11.0 1.0 N A:SER49 4.0 11.0 1.0 N4 A:M4U402 4.2 16.2 1.0 C A:ALA47 4.3 12.9 1.0 C15 A:M4U402 4.3 14.4 1.0 O A:ALA47 4.4 12.6 1.0 C2 A:M4U402 4.6 13.5 1.0 CA A:ALA47 4.6 15.8 1.0 N A:VAL48 4.6 11.7 1.0 CG A:LEU321 4.7 16.1 1.0 CG2 A:ILE305 4.8 10.5 1.0 CA A:VAL48 4.9 12.0 1.0 C A:SER49 5.0 13.2 1.0 C5 A:M4U402 5.0 9.7 1.0

Fluorine binding site 2 out of 3 in the WDR5 Bound to 2-(3,5-Dimethoxybenzyl)-7-((2-Methyl-1H-Imidazol-1-Yl) Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-3,4- Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of WDR5 Bound to 2-(3,5-Dimethoxybenzyl)-7-((2-Methyl-1H-Imidazol-1-Yl) Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-3,4- Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:F402 b:21.1 occ:1.00 F2 A:M4U402 0.0 21.1 1.0 C20 A:M4U402 1.3 21.1 1.0 F1 A:M4U402 2.1 20.1 1.0 F3 A:M4U402 2.1 19.6 1.0 C14 A:M4U402 2.4 16.7 1.0 C10 A:M4U402 3.0 15.0 1.0 C1 A:M4U402 3.1 10.8 1.0 C2 A:M4U402 3.3 13.5 1.0 CD2 A:LEU321 3.3 13.2 1.0 C7 A:M4U402 3.4 13.8 1.0 N3 A:M4U402 3.5 16.2 1.0 C6 A:M4U402 3.8 11.0 1.0 C3 A:M4U402 4.1 10.5 1.0 C15 A:M4U402 4.2 14.4 1.0 O A:HOH715 4.3 42.2 1.0 N4 A:M4U402 4.4 16.2 1.0 CG A:LEU321 4.6 16.1 1.0 C5 A:M4U402 4.6 9.7 1.0 CB A:ALA47 4.6 18.6 1.0 O A:HOH723 4.6 19.3 1.0 CD1 A:LEU321 4.7 14.4 1.0 C4 A:M4U402 4.7 11.3 1.0 CD1 A:ILE305 4.8 12.9 1.0 C8 A:M4U402 4.9 13.6 1.0 O A:HOH722 4.9 39.7 1.0 CE1 A:TYR260 5.0 20.7 1.0 C9 A:M4U402 5.0 11.8 1.0

Fluorine binding site 3 out of 3 in the WDR5 Bound to 2-(3,5-Dimethoxybenzyl)-7-((2-Methyl-1H-Imidazol-1-Yl) Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-3,4- Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of WDR5 Bound to 2-(3,5-Dimethoxybenzyl)-7-((2-Methyl-1H-Imidazol-1-Yl) Methyl)-5-(1-Methyl-3-(Trifluoromethyl)-1H-Pyrazol-4-Yl)-3,4- Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:F402 b:19.6 occ:1.00 F3 A:M4U402 0.0 19.6 1.0 C20 A:M4U402 1.3 21.1 1.0 F2 A:M4U402 2.1 21.1 1.0 F1 A:M4U402 2.1 20.1 1.0 C14 A:M4U402 2.3 16.7 1.0 N3 A:M4U402 2.6 16.2 1.0 CB A:ALA47 3.2 18.6 1.0 O A:HOH722 3.3 39.7 1.0 C10 A:M4U402 3.6 15.0 1.0 N4 A:M4U402 4.0 16.2 1.0 O A:HOH723 4.1 19.3 1.0 CD2 A:LEU321 4.1 13.2 1.0 CB A:ALA65 4.2 16.9 1.0 C15 A:M4U402 4.4 14.4 1.0 C1 A:M4U402 4.5 10.8 1.0 CA A:ALA47 4.6 15.8 1.0 O A:HOH715 4.6 42.2 1.0 O A:ALA47 4.8 12.6 1.0 C7 A:M4U402 4.8 13.8 1.0 C A:ALA47 4.8 12.9 1.0 C2 A:M4U402 4.9 13.5 1.0

K.B.Teuscher, K.M.Meyers, Q.Wei, J.J.Mills, J.Tian, J.Alvarado, J.Sai, M.Van Meveren, T.M.South, T.A.Rietz, B.Zhao, W.J.Moore, G.M.Stott, W.P.Tansey, T.Lee, S.W.Fesik. Discovery of Potent Orally Bioavailable Wd Repeat Domain 5 (WDR5) Inhibitors Using A Pharmacophore-Based Optimization. J.Med.Chem. V. 65 6287 2022.
ISSN: ISSN 0022-2623
PubMed: 35436124
DOI: 10.1021/ACS.JMEDCHEM.2C00195