Fluorine in PDB 8g3e: Crystal Structure of Human WDR5 in Complex with (1M)-N-[(3,5- Difluoro[1,1'-Biphenyl]-4-Yl)Methyl]-6-Methyl-4-Oxo-1-(Pyridin-3-Yl)- 1,4-Dihydropyridazine-3-Carboxamide (Compound 2, WDR5-Myc Inhibitor)

The structure of Crystal Structure of Human WDR5 in Complex with (1M)-N-[(3,5- Difluoro[1,1'-Biphenyl]-4-Yl)Methyl]-6-Methyl-4-Oxo-1-(Pyridin-3-Yl)- 1,4-Dihydropyridazine-3-Carboxamide (Compound 2, WDR5-Myc Inhibitor), PDB code: 8g3e was solved by M.Zhao, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	32.35 / 1.33
Space group	P 1
Cell size a, b, c (Å), α, β, γ (°)	46.662, 62.276, 64.381, 114.09, 91.08, 110.17
R / Rfree (%)	13.9 / 17

The binding sites of Fluorine atom in the Crystal Structure of Human WDR5 in Complex with (1M)-N-[(3,5- Difluoro[1,1'-Biphenyl]-4-Yl)Methyl]-6-Methyl-4-Oxo-1-(Pyridin-3-Yl)- 1,4-Dihydropyridazine-3-Carboxamide (Compound 2, WDR5-Myc Inhibitor) (pdb code 8g3e). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the Crystal Structure of Human WDR5 in Complex with (1M)-N-[(3,5- Difluoro[1,1'-Biphenyl]-4-Yl)Methyl]-6-Methyl-4-Oxo-1-(Pyridin-3-Yl)- 1,4-Dihydropyridazine-3-Carboxamide (Compound 2, WDR5-Myc Inhibitor), PDB code: 8g3e:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in the Crystal Structure of Human WDR5 in Complex with (1M)-N-[(3,5- Difluoro[1,1'-Biphenyl]-4-Yl)Methyl]-6-Methyl-4-Oxo-1-(Pyridin-3-Yl)- 1,4-Dihydropyridazine-3-Carboxamide (Compound 2, WDR5-Myc Inhibitor)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Crystal Structure of Human WDR5 in Complex with (1M)-N-[(3,5- Difluoro[1,1'-Biphenyl]-4-Yl)Methyl]-6-Methyl-4-Oxo-1-(Pyridin-3-Yl)- 1,4-Dihydropyridazine-3-Carboxamide (Compound 2, WDR5-Myc Inhibitor) within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:32.9 occ:1.00 F15 A:YJR401 0.0 32.9 1.0 C2 A:YJR401 1.3 31.0 1.0 C3 A:YJR401 2.3 36.6 1.0 C1 A:YJR401 2.4 30.4 1.0 C13 A:YJR401 2.9 28.9 1.0 N14 A:YJR401 3.1 28.9 1.0 CG A:LYS272 3.5 25.6 1.0 C4 A:YJR401 3.6 35.5 1.0 C6 A:YJR401 3.6 29.6 1.0 CB A:LYS272 3.7 24.1 1.0 O25 A:YJR401 3.8 35.6 1.0 CD A:LYS272 3.9 27.0 1.0 CD1 A:LEU288 4.1 24.3 1.0 C5 A:YJR401 4.1 33.7 1.0 C17 A:YJR401 4.2 31.9 1.0 NZ A:LYS272 4.3 37.9 1.0 O A:HOH674 4.4 22.4 1.0 CD2 A:LEU288 4.6 25.3 1.0 C24 A:YJR401 4.6 38.1 1.0 CE A:LYS272 4.7 31.8 1.0 F16 A:YJR401 4.8 32.9 1.0 C18 A:YJR401 4.9 34.4 1.0 CG A:LEU288 4.9 23.8 1.0 C7 A:YJR401 4.9 39.8 1.0 CA A:LYS272 5.0 22.0 1.0

Fluorine binding site 2 out of 4 in the Crystal Structure of Human WDR5 in Complex with (1M)-N-[(3,5- Difluoro[1,1'-Biphenyl]-4-Yl)Methyl]-6-Methyl-4-Oxo-1-(Pyridin-3-Yl)- 1,4-Dihydropyridazine-3-Carboxamide (Compound 2, WDR5-Myc Inhibitor)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Crystal Structure of Human WDR5 in Complex with (1M)-N-[(3,5- Difluoro[1,1'-Biphenyl]-4-Yl)Methyl]-6-Methyl-4-Oxo-1-(Pyridin-3-Yl)- 1,4-Dihydropyridazine-3-Carboxamide (Compound 2, WDR5-Myc Inhibitor) within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:32.9 occ:1.00 F16 A:YJR401 0.0 32.9 1.0 C6 A:YJR401 1.3 29.6 1.0 C5 A:YJR401 2.3 33.7 1.0 C1 A:YJR401 2.4 30.4 1.0 C13 A:YJR401 2.8 28.9 1.0 CB A:SER223 3.1 20.3 1.0 CE2 A:PHE266 3.3 20.0 1.0 CD2 A:TYR228 3.4 29.1 1.0 C4 A:YJR401 3.6 35.5 1.0 C2 A:YJR401 3.6 31.0 1.0 O19 A:YJR401 3.6 30.9 1.0 CD2 A:PHE266 3.7 18.2 1.0 OG A:SER223 3.7 22.0 1.0 N14 A:YJR401 3.9 28.9 1.0 CE2 A:TYR228 4.1 30.6 1.0 C3 A:YJR401 4.1 36.6 1.0 CZ A:PHE266 4.1 18.8 1.0 C17 A:YJR401 4.2 31.9 1.0 CG A:TYR228 4.2 27.9 1.0 CB A:TYR228 4.3 25.0 1.0 ND2 A:ASN225 4.3 35.8 1.0 CD1 A:LEU288 4.3 24.3 1.0 CA A:SER223 4.4 18.7 1.0 OD1 A:ASN225 4.4 28.2 1.0 CD1 A:LEU240 4.5 20.2 1.0 CG A:ASN225 4.6 31.8 1.0 CD2 A:LEU240 4.7 25.3 1.0 F15 A:YJR401 4.8 32.9 1.0 CG A:PHE266 4.8 17.1 1.0 C7 A:YJR401 4.8 39.8 1.0 CD A:PRO224 4.9 23.3 1.0

Fluorine binding site 3 out of 4 in the Crystal Structure of Human WDR5 in Complex with (1M)-N-[(3,5- Difluoro[1,1'-Biphenyl]-4-Yl)Methyl]-6-Methyl-4-Oxo-1-(Pyridin-3-Yl)- 1,4-Dihydropyridazine-3-Carboxamide (Compound 2, WDR5-Myc Inhibitor)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Crystal Structure of Human WDR5 in Complex with (1M)-N-[(3,5- Difluoro[1,1'-Biphenyl]-4-Yl)Methyl]-6-Methyl-4-Oxo-1-(Pyridin-3-Yl)- 1,4-Dihydropyridazine-3-Carboxamide (Compound 2, WDR5-Myc Inhibitor) within 5.0Å range: probe atom residue distance (Å) B Occ B:F401 b:37.2 occ:1.00 F15 B:YJR401 0.0 37.2 1.0 C2 B:YJR401 1.3 32.7 1.0 C3 B:YJR401 2.4 34.4 1.0 C1 B:YJR401 2.4 30.8 1.0 C13 B:YJR401 2.9 31.6 1.0 N14 B:YJR401 3.1 31.0 1.0 C6 B:YJR401 3.6 28.3 1.0 CG B:LYS272 3.6 23.6 1.0 C4 B:YJR401 3.7 32.9 1.0 O25 B:YJR401 3.7 35.5 1.0 CB B:LYS272 3.8 21.3 1.0 CD B:LYS272 3.9 27.9 1.0 CD1 B:LEU288 4.0 23.3 1.0 C5 B:YJR401 4.1 30.3 1.0 O B:HOH663 4.2 21.9 1.0 C17 B:YJR401 4.3 35.5 1.0 NZ B:LYS272 4.3 39.1 1.0 O B:HOH751 4.6 50.4 1.0 CD2 B:LEU288 4.7 23.9 1.0 C24 B:YJR401 4.7 42.7 1.0 F16 B:YJR401 4.7 31.2 1.0 CE B:LYS272 4.8 32.9 1.0 CG B:LEU288 4.8 22.2 1.0 C7 B:YJR401 4.9 34.8 1.0

Fluorine binding site 4 out of 4 in the Crystal Structure of Human WDR5 in Complex with (1M)-N-[(3,5- Difluoro[1,1'-Biphenyl]-4-Yl)Methyl]-6-Methyl-4-Oxo-1-(Pyridin-3-Yl)- 1,4-Dihydropyridazine-3-Carboxamide (Compound 2, WDR5-Myc Inhibitor)


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Crystal Structure of Human WDR5 in Complex with (1M)-N-[(3,5- Difluoro[1,1'-Biphenyl]-4-Yl)Methyl]-6-Methyl-4-Oxo-1-(Pyridin-3-Yl)- 1,4-Dihydropyridazine-3-Carboxamide (Compound 2, WDR5-Myc Inhibitor) within 5.0Å range: probe atom residue distance (Å) B Occ B:F401 b:31.2 occ:1.00 F16 B:YJR401 0.0 31.2 1.0 C6 B:YJR401 1.3 28.3 1.0 C5 B:YJR401 2.3 30.3 1.0 C1 B:YJR401 2.4 30.8 1.0 C13 B:YJR401 2.8 31.6 1.0 CB B:SER223 3.1 20.1 1.0 CD2 B:TYR228 3.2 27.6 1.0 CE2 B:PHE266 3.3 18.3 1.0 CB B:TYR228 3.6 21.4 1.0 OG B:SER223 3.6 21.5 1.0 C2 B:YJR401 3.6 32.7 1.0 C4 B:YJR401 3.6 32.9 1.0 CG B:TYR228 3.7 24.1 1.0 CD2 B:PHE266 3.8 17.7 1.0 O19 B:YJR401 3.8 34.8 1.0 N14 B:YJR401 3.9 31.0 1.0 CZ B:PHE266 4.0 16.8 1.0 CE2 B:TYR228 4.1 28.5 1.0 C3 B:YJR401 4.1 34.4 1.0 C17 B:YJR401 4.3 35.5 1.0 CD1 B:LEU240 4.3 23.0 1.0 CA B:SER223 4.5 18.8 1.0 OD1 B:ASN225 4.6 30.8 1.0 CD1 B:LEU288 4.7 23.3 1.0 F15 B:YJR401 4.7 37.2 1.0 ND2 B:ASN225 4.8 40.4 1.0 CD1 B:TYR228 4.8 25.8 1.0 CG B:PHE266 4.8 16.5 1.0 C7 B:YJR401 4.8 34.8 1.0 O B:HOH751 4.9 50.4 1.0 CA B:TYR228 4.9 20.4 1.0 CD2 B:LEU240 4.9 25.5 1.0 CE1 B:PHE266 5.0 16.6 1.0

J.Ding, L.Liu, Y.L.Chiang, M.Zhao, H.Liu, F.Yang, L.Shen, Y.Lin, H.Deng, J.Gao, D.R.Sage, L.West, L.A.Llamas, X.Hao, S.Kawatkar, E.Li, R.K.Jain, J.A.Tallarico, S.M.Canham, H.Wang. Discovery and Structure-Based Design of Inhibitors of the Wd Repeat-Containing Protein 5 (WDR5)-Myc Interaction. J.Med.Chem. 2023.
ISSN: ISSN 0022-2623
PubMed: 37307526
DOI: 10.1021/ACS.JMEDCHEM.3C00787