Fluorine in PDB 7uzn: Crystal Structure of the First Bromodomain of Human BRD4 in Complex with Bmt-206059 Aka 2-{(3M)-3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-8- Fluoro-5-[(S)-(Oxan-4-Yl)(Phenyl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol, Triply Deuterated on the 4-Methyl Group

The structure of Crystal Structure of the First Bromodomain of Human BRD4 in Complex with Bmt-206059 Aka 2-{(3M)-3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-8- Fluoro-5-[(S)-(Oxan-4-Yl)(Phenyl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol, Triply Deuterated on the 4-Methyl Group, PDB code: 7uzn was solved by S.Sheriff, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	16.96 / 1.69
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	41.549, 46.168, 58.745, 90, 90, 90
R / Rfree (%)	19.7 / 21.7

The structure of Crystal Structure of the First Bromodomain of Human BRD4 in Complex with Bmt-206059 Aka 2-{(3M)-3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-8- Fluoro-5-[(S)-(Oxan-4-Yl)(Phenyl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol, Triply Deuterated on the 4-Methyl Group also contains other interesting chemical elements:

Sodium

(Na)

1 atom

The binding sites of Fluorine atom in the Crystal Structure of the First Bromodomain of Human BRD4 in Complex with Bmt-206059 Aka 2-{(3M)-3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-8- Fluoro-5-[(S)-(Oxan-4-Yl)(Phenyl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol, Triply Deuterated on the 4-Methyl Group (pdb code 7uzn). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total only one binding site of Fluorine was determined in the Crystal Structure of the First Bromodomain of Human BRD4 in Complex with Bmt-206059 Aka 2-{(3M)-3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-8- Fluoro-5-[(S)-(Oxan-4-Yl)(Phenyl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol, Triply Deuterated on the 4-Methyl Group, PDB code: 7uzn:

Fluorine binding site 1 out of 1 in the Crystal Structure of the First Bromodomain of Human BRD4 in Complex with Bmt-206059 Aka 2-{(3M)-3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-8- Fluoro-5-[(S)-(Oxan-4-Yl)(Phenyl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol, Triply Deuterated on the 4-Methyl Group


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 Bmt-206059 Aka 2-{(3M)-3-(1,4-Dimethyl-1H-1,2,3-Triazol-5-Yl)-8- Fluoro-5-[(S)-(Oxan-4-Yl)(Phenyl)Methyl]-5H-Pyrido[3,2-B]Indol-7- Yl}Propan-2-Ol, Triply Deuterated on the 4-Methyl Group within 5.0Å range: probe atom residue distance (Å) B Occ A:F201 b:22.0 occ:1.00 F38 A:PQF201 0.0 22.0 1.0 C17 A:PQF201 1.3 21.5 1.0 C6 A:PQF201 2.3 20.5 1.0 C13 A:PQF201 2.4 21.3 1.0 H62 A:PQF201 2.4 21.6 0.0 H64 A:PQF201 2.4 20.8 0.0 H44 A:PQF201 2.5 20.5 0.0 C30 A:PQF201 2.9 21.4 1.0 C27 A:PQF201 3.1 20.8 1.0 C26 A:PQF201 3.1 21.6 1.0 HZ3 A:TRP81 3.5 19.8 0.0 C10 A:PQF201 3.6 20.2 1.0 C8 A:PQF201 3.6 20.8 1.0 H61 A:PQF201 3.6 21.6 0.0 H65 A:PQF201 3.6 20.8 0.0 HD21 A:LEU92 3.8 28.4 0.0 H60 A:PQF201 3.9 21.6 0.0 H63 A:PQF201 3.9 20.8 0.0 C16 A:PQF201 4.1 20.5 1.0 O37 A:PQF201 4.3 21.8 1.0 HE3 A:TRP81 4.5 19.0 0.0 CZ3 A:TRP81 4.5 19.8 1.0 H46 A:PQF201 4.5 20.8 0.0 CD2 A:LEU92 4.8 28.4 1.0 H70 A:PQF201 4.8 21.8 0.0 O A:HOH335 4.9 31.1 1.0 C14 A:PQF201 4.9 19.5 1.0 CE3 A:TRP81 5.0 19.0 1.0 HD23 A:LEU92 5.0 28.4 0.0

M.D.Hill, H.Fang, D.Norris, G.V.Delucca, H.Huang, M.Debenedetto, C.Quesnelle, W.D.Schmitz, J.S.Tokarski, S.Sheriff, C.Yan, C.Fanslau, Z.Haarhoff, C.Huang, M.Kramer, S.Madari, K.Menard, L.Monereau, J.Morrison, N.Raghavan, E.E.Shields, J.Simmermacher-Mayer, M.Sinz, C.K.Tye, R.Westhouse, C.Xie, H.Zhang, L.Zhang, T.Zvyaga, F.Lee, A.V.Gavai, A.P.Degnan. Development of Bet Inhibitors As Potential Treatments For Cancer: Optimization of Pharmacokinetic Properties. Acs Med.Chem.Lett. V. 13 1165 2022.
ISSN: ISSN 1948-5875
PubMed: 35859878
DOI: 10.1021/ACSMEDCHEMLETT.2C00219