Fluorine in PDB 7mcf: Crystal Structure of the First Bromodomain of Human BRD4 in Complex with 2-{3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-6-Fluoro-5-[(S)-(3- Fluoropyridin-2-Yl)(Oxan-4-Yl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol

The structure of Crystal Structure of the First Bromodomain of Human BRD4 in Complex with 2-{3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-6-Fluoro-5-[(S)-(3- Fluoropyridin-2-Yl)(Oxan-4-Yl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol, PDB code: 7mcf was solved by S.Sheriff, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	19.89 / 2.19
Space group	P 21 21 2
Cell size a, b, c (Å), α, β, γ (°)	87.912, 89.356, 36.554, 90, 90, 90
R / Rfree (%)	20.4 / 23.4

The binding sites of Fluorine atom in the Crystal Structure of the First Bromodomain of Human BRD4 in Complex with 2-{3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-6-Fluoro-5-[(S)-(3- Fluoropyridin-2-Yl)(Oxan-4-Yl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol (pdb code 7mcf). 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 the First Bromodomain of Human BRD4 in Complex with 2-{3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-6-Fluoro-5-[(S)-(3- Fluoropyridin-2-Yl)(Oxan-4-Yl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol, PDB code: 7mcf:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in the Crystal Structure of the First Bromodomain of Human BRD4 in Complex with 2-{3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-6-Fluoro-5-[(S)-(3- Fluoropyridin-2-Yl)(Oxan-4-Yl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol


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 the First Bromodomain of Human BRD4 in Complex with 2-{3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-6-Fluoro-5-[(S)-(3- Fluoropyridin-2-Yl)(Oxan-4-Yl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol within 5.0Å range: probe atom residue distance (Å) B Occ A:F301 b:24.6 occ:1.00 F34 A:YX4301 0.0 24.6 1.0 C9 A:YX4301 1.3 22.2 1.0 H59 A:YX4301 2.2 24.6 0.0 C2 A:YX4301 2.3 22.2 1.0 C8 A:YX4301 2.3 25.5 1.0 H69 A:YX4301 2.5 26.6 0.0 H63 A:YX4301 2.5 28.6 0.0 F37 A:YX4301 2.6 22.8 1.0 C15 A:YX4301 2.9 28.1 1.0 N3 A:YX4301 3.0 23.1 1.0 C27 A:YX4301 3.0 24.5 1.0 C38 A:YX4301 3.1 26.5 1.0 C35 A:YX4301 3.1 28.6 1.0 H67 A:YX4301 3.4 26.6 0.0 H58 A:YX4301 3.4 25.9 0.0 H65 A:YX4301 3.5 28.6 0.0 C29 A:YX4301 3.6 24.3 1.0 C7 A:YX4301 3.6 24.0 1.0 C1 A:YX4301 3.6 22.9 1.0 C28 A:YX4301 3.8 26.2 1.0 CH2 A:TRP81 4.0 22.8 1.0 H64 A:YX4301 4.0 28.6 0.0 H68 A:YX4301 4.0 26.6 0.0 C25 A:YX4301 4.1 24.8 1.0 C6 A:YX4301 4.1 23.9 1.0 C26 A:YX4301 4.1 25.9 1.0 CD2 A:LEU92 4.2 23.0 1.0 H54 A:YX4301 4.2 23.9 0.0 H57 A:YX4301 4.3 25.9 0.0 C4 A:YX4301 4.3 20.6 1.0 O36 A:YX4301 4.3 29.1 1.0 CZ3 A:TRP81 4.5 22.4 1.0 H44 A:YX4301 4.5 24.1 0.0 C5 A:YX4301 4.6 22.1 1.0 C24 A:YX4301 4.7 23.9 1.0 C30 A:YX4301 4.9 24.1 1.0 H66 A:YX4301 4.9 29.1 0.0

Fluorine binding site 2 out of 4 in the Crystal Structure of the First Bromodomain of Human BRD4 in Complex with 2-{3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-6-Fluoro-5-[(S)-(3- Fluoropyridin-2-Yl)(Oxan-4-Yl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol


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 the First Bromodomain of Human BRD4 in Complex with 2-{3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-6-Fluoro-5-[(S)-(3- Fluoropyridin-2-Yl)(Oxan-4-Yl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol within 5.0Å range: probe atom residue distance (Å) B Occ A:F301 b:22.8 occ:1.00 F37 A:YX4301 0.0 22.8 1.0 C29 A:YX4301 1.3 24.3 1.0 C30 A:YX4301 2.4 24.1 1.0 H59 A:YX4301 2.4 24.6 0.0 C28 A:YX4301 2.4 26.2 1.0 H60 A:YX4301 2.6 24.2 0.0 F34 A:YX4301 2.6 24.6 1.0 C27 A:YX4301 2.8 24.5 1.0 C9 A:YX4301 3.5 22.2 1.0 N3 A:YX4301 3.5 23.1 1.0 N33 A:YX4301 3.6 28.7 1.0 C31 A:YX4301 3.6 27.7 1.0 H63 A:YX4301 3.6 28.6 0.0 C2 A:YX4301 3.8 22.2 1.0 H54 A:YX4301 3.9 23.9 0.0 CD2 A:LEU92 4.0 23.0 1.0 C32 A:YX4301 4.1 27.4 1.0 C25 A:YX4301 4.2 24.8 1.0 H55 A:YX4301 4.2 23.9 0.0 C24 A:YX4301 4.3 23.9 1.0 H61 A:YX4301 4.5 27.7 0.0 C35 A:YX4301 4.5 28.6 1.0 H65 A:YX4301 4.6 28.6 0.0 C8 A:YX4301 4.6 25.5 1.0 H58 A:YX4301 4.7 25.9 0.0 H69 A:YX4301 4.7 26.6 0.0 C4 A:YX4301 4.7 20.6 1.0 H56 A:YX4301 4.9 24.8 0.0 CG A:LEU92 4.9 27.0 1.0

Fluorine binding site 3 out of 4 in the Crystal Structure of the First Bromodomain of Human BRD4 in Complex with 2-{3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-6-Fluoro-5-[(S)-(3- Fluoropyridin-2-Yl)(Oxan-4-Yl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol


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 the First Bromodomain of Human BRD4 in Complex with 2-{3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-6-Fluoro-5-[(S)-(3- Fluoropyridin-2-Yl)(Oxan-4-Yl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol within 5.0Å range: probe atom residue distance (Å) B Occ A:F302 b:20.7 occ:1.00 F34 A:YX4302 0.0 20.7 1.0 C9 A:YX4302 1.4 22.5 1.0 H59 A:YX4302 2.2 28.5 0.0 C2 A:YX4302 2.4 21.6 1.0 C8 A:YX4302 2.4 23.2 1.0 H69 A:YX4302 2.5 23.9 0.0 H63 A:YX4302 2.6 25.8 0.0 F37 A:YX4302 2.7 47.8 1.0 C15 A:YX4302 2.9 25.1 1.0 C27 A:YX4302 3.0 28.5 1.0 N3 A:YX4302 3.0 24.4 1.0 C38 A:YX4302 3.0 23.9 1.0 C35 A:YX4302 3.1 25.8 1.0 H67 A:YX4302 3.3 23.9 0.0 H58 A:YX4302 3.3 25.6 0.0 H65 A:YX4302 3.6 25.8 0.0 C29 A:YX4302 3.6 40.7 1.0 C7 A:YX4302 3.6 23.9 1.0 C1 A:YX4302 3.6 23.7 1.0 CG2 A:ILE126 3.7 23.6 1.0 C28 A:YX4302 3.7 37.5 1.0 H68 A:YX4302 4.0 23.9 0.0 CE2 A:PHE157 4.0 28.9 1.0 C25 A:YX4302 4.0 26.7 1.0 C26 A:YX4302 4.0 25.5 1.0 H64 A:YX4302 4.1 25.8 0.0 H54 A:YX4302 4.1 27.0 0.0 C6 A:YX4302 4.1 22.9 1.0 CD1 A:ILE161 4.1 54.9 1.0 H57 A:YX4302 4.2 25.6 0.0 CH2 B:TRP81 4.3 22.7 1.0 O36 A:YX4302 4.3 28.4 1.0 C4 A:YX4302 4.3 24.8 1.0 CD2 B:LEU92 4.4 37.2 1.0 H44 A:YX4302 4.5 23.9 0.0 C24 A:YX4302 4.6 26.9 1.0 C5 A:YX4302 4.6 24.8 1.0 CD2 A:LEU158 4.7 25.9 1.0 CZ3 B:TRP81 4.8 22.3 1.0 CZ A:PHE157 4.8 26.4 1.0 C30 A:YX4302 4.9 42.2 1.0 H66 A:YX4302 4.9 28.5 0.0 CD2 A:PHE157 4.9 26.3 1.0 H56 A:YX4302 4.9 26.7 0.0

Fluorine binding site 4 out of 4 in the Crystal Structure of the First Bromodomain of Human BRD4 in Complex with 2-{3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-6-Fluoro-5-[(S)-(3- Fluoropyridin-2-Yl)(Oxan-4-Yl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol


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 the First Bromodomain of Human BRD4 in Complex with 2-{3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-6-Fluoro-5-[(S)-(3- Fluoropyridin-2-Yl)(Oxan-4-Yl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol within 5.0Å range: probe atom residue distance (Å) B Occ A:F302 b:47.8 occ:1.00 F37 A:YX4302 0.0 47.8 1.0 C29 A:YX4302 1.3 40.7 1.0 C30 A:YX4302 2.3 42.2 1.0 C28 A:YX4302 2.4 37.5 1.0 H59 A:YX4302 2.4 28.5 0.0 H60 A:YX4302 2.6 42.2 0.0 F34 A:YX4302 2.7 20.7 1.0 CD1 A:ILE161 2.9 54.9 1.0 C27 A:YX4302 2.9 28.5 1.0 CD2 A:LEU158 3.2 25.9 1.0 C9 A:YX4302 3.4 22.5 1.0 N3 A:YX4302 3.5 24.4 1.0 C31 A:YX4302 3.5 41.8 1.0 H63 A:YX4302 3.6 25.8 0.0 N33 A:YX4302 3.6 41.4 1.0 C2 A:YX4302 3.7 21.6 1.0 CG1 A:ILE161 3.9 44.8 1.0 CD2 B:LEU92 4.0 37.2 1.0 C32 A:YX4302 4.0 42.7 1.0 H54 A:YX4302 4.0 27.0 0.0 C25 A:YX4302 4.2 26.7 1.0 H55 A:YX4302 4.3 27.0 0.0 C24 A:YX4302 4.4 26.9 1.0 H61 A:YX4302 4.4 41.9 0.0 C35 A:YX4302 4.4 25.8 1.0 H65 A:YX4302 4.5 25.8 0.0 C8 A:YX4302 4.5 23.2 1.0 CE2 A:PHE157 4.6 28.9 1.0 CG A:LEU158 4.6 26.5 1.0 H69 A:YX4302 4.6 23.9 0.0 C4 A:YX4302 4.7 24.8 1.0 H58 A:YX4302 4.8 25.6 0.0 H56 A:YX4302 4.9 26.7 0.0 C15 A:YX4302 5.0 25.1 1.0 C1 A:YX4302 5.0 23.7 1.0 CG B:LEU92 5.0 36.7 1.0

M.D.Hill, H.Fang, J.Tokarski, C.Fanslau, Z.Haarhoff, C.Huang, M.Kramer, K.Menard, L.Monereau, J.Morrison, A.Ranasinghe, E.E.Shields, C.K.Tye, R.Westhouse, G.Everlof, S.Sheriff, C.Yan, F.Marsilio, L.Zhang, T.Zvyaga, F.Lee, A.V.Gavai, A.P.Degnan. Development of Bet Inhibitors As Potential Treatments For Cancer: A Search For Structural Diversity. Bioorg.Med.Chem.Lett. 28108 2021.
ISSN: ESSN 1464-3405
PubMed: 33991625
DOI: 10.1016/J.BMCL.2021.128108