Fluorine in PDB 8ck4: Structure of HIF2A-Arnt Heterodimer in Complex with (4S)-1-(3,5- Difluorophenyl)-5,5-Difluoro-3-Methanesulfonyl-4,5,6,7-Tetrahydro-2- Benzothiophen-4-Ol

The structure of Structure of HIF2A-Arnt Heterodimer in Complex with (4S)-1-(3,5- Difluorophenyl)-5,5-Difluoro-3-Methanesulfonyl-4,5,6,7-Tetrahydro-2- Benzothiophen-4-Ol, PDB code: 8ck4 was solved by D.Musil, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	41.88 / 2.29
Space group	C 1 2 1
Cell size a, b, c (Å), α, β, γ (°)	72.287, 83.765, 41.149, 90, 106.59, 90
R / Rfree (%)	20.9 / 25.1

The binding sites of Fluorine atom in the Structure of HIF2A-Arnt Heterodimer in Complex with (4S)-1-(3,5- Difluorophenyl)-5,5-Difluoro-3-Methanesulfonyl-4,5,6,7-Tetrahydro-2- Benzothiophen-4-Ol (pdb code 8ck4). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the Structure of HIF2A-Arnt Heterodimer in Complex with (4S)-1-(3,5- Difluorophenyl)-5,5-Difluoro-3-Methanesulfonyl-4,5,6,7-Tetrahydro-2- Benzothiophen-4-Ol, PDB code: 8ck4:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in the Structure of HIF2A-Arnt Heterodimer in Complex with (4S)-1-(3,5- Difluorophenyl)-5,5-Difluoro-3-Methanesulfonyl-4,5,6,7-Tetrahydro-2- Benzothiophen-4-Ol


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Structure of HIF2A-Arnt Heterodimer in Complex with (4S)-1-(3,5- Difluorophenyl)-5,5-Difluoro-3-Methanesulfonyl-4,5,6,7-Tetrahydro-2- Benzothiophen-4-Ol within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:50.4 occ:1.00 F15 A:UY3401 0.0 50.4 1.0 C11 A:UY3401 1.4 50.5 1.0 F16 A:UY3401 2.2 50.0 1.0 C5 A:UY3401 2.3 51.0 1.0 C7 A:UY3401 2.3 50.3 1.0 H27 A:UY3401 2.4 51.0 0.0 H29 A:UY3401 2.6 50.3 0.0 H26 A:UY3401 2.7 50.5 0.0 C3 A:UY3401 2.9 50.5 1.0 C2 A:UY3401 3.1 51.9 1.0 CG2 A:ILE337 3.2 41.1 1.0 H28 A:UY3401 3.3 50.3 0.0 C1 A:UY3401 3.3 51.3 1.0 CD1 A:ILE337 3.5 42.2 1.0 O10 A:UY3401 3.6 50.8 1.0 CB A:ILE337 3.6 41.4 1.0 SG A:CYS339 3.6 44.4 1.0 H30 A:UY3401 3.7 50.8 0.0 CB A:HIS248 3.8 39.3 1.0 CG A:HIS248 3.8 40.2 1.0 H25 A:UY3401 3.9 50.5 0.0 CD2 A:HIS248 4.0 40.6 1.0 CG1 A:ILE337 4.1 41.5 1.0 C6 A:UY3401 4.3 53.5 1.0 H33 A:UY3401 4.4 56.4 0.0 CD2 A:LEU296 4.4 61.4 1.0 ND1 A:HIS248 4.5 41.2 1.0 C4 A:UY3401 4.6 51.5 1.0 NE2 A:HIS248 4.7 41.0 1.0 ND1 A:HIS293 4.8 56.5 1.0 CE1 A:HIS248 4.9 41.2 1.0 H35 A:UY3401 5.0 56.4 0.0 CA A:ILE337 5.0 41.9 1.0 CA A:MET252 5.0 46.3 1.0 O A:ILE337 5.0 40.1 1.0

Fluorine binding site 2 out of 4 in the Structure of HIF2A-Arnt Heterodimer in Complex with (4S)-1-(3,5- Difluorophenyl)-5,5-Difluoro-3-Methanesulfonyl-4,5,6,7-Tetrahydro-2- Benzothiophen-4-Ol


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Structure of HIF2A-Arnt Heterodimer in Complex with (4S)-1-(3,5- Difluorophenyl)-5,5-Difluoro-3-Methanesulfonyl-4,5,6,7-Tetrahydro-2- Benzothiophen-4-Ol within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:50.0 occ:1.00 F16 A:UY3401 0.0 50.0 1.0 C11 A:UY3401 1.4 50.5 1.0 F15 A:UY3401 2.2 50.4 1.0 C7 A:UY3401 2.3 50.3 1.0 C5 A:UY3401 2.4 51.0 1.0 H30 A:UY3401 2.4 50.8 0.0 H29 A:UY3401 2.6 50.3 0.0 H28 A:UY3401 2.6 50.3 0.0 O10 A:UY3401 2.7 50.8 1.0 H27 A:UY3401 2.8 51.0 0.0 ND1 A:HIS293 3.0 56.5 1.0 CE1 A:HIS293 3.1 56.7 1.0 CG A:MET252 3.3 50.9 1.0 CD1 A:ILE337 3.3 42.2 1.0 C2 A:UY3401 3.7 51.9 1.0 C3 A:UY3401 3.7 50.5 1.0 CA A:MET252 3.8 46.3 1.0 CB A:MET252 3.9 47.6 1.0 H26 A:UY3401 4.1 50.5 0.0 C1 A:UY3401 4.2 51.3 1.0 N A:MET252 4.3 47.3 1.0 CG A:HIS293 4.3 55.2 1.0 NE2 A:HIS293 4.4 56.8 1.0 H25 A:UY3401 4.5 50.5 0.0 CG1 A:ILE337 4.5 41.5 1.0 CD2 A:LEU296 4.6 61.4 1.0 O A:SER249 4.6 47.1 1.0 CG2 A:ILE337 4.6 41.1 1.0 CB A:HIS248 4.7 39.3 1.0 SD A:MET252 4.7 60.2 1.0 CB A:ILE337 4.7 41.4 1.0 CE A:MET252 4.8 60.5 1.0 C6 A:UY3401 4.9 53.5 1.0 C A:MET252 4.9 44.5 1.0 CG A:HIS248 5.0 40.2 1.0 CD2 A:HIS293 5.0 56.0 1.0

Fluorine binding site 3 out of 4 in the Structure of HIF2A-Arnt Heterodimer in Complex with (4S)-1-(3,5- Difluorophenyl)-5,5-Difluoro-3-Methanesulfonyl-4,5,6,7-Tetrahydro-2- Benzothiophen-4-Ol


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Structure of HIF2A-Arnt Heterodimer in Complex with (4S)-1-(3,5- Difluorophenyl)-5,5-Difluoro-3-Methanesulfonyl-4,5,6,7-Tetrahydro-2- Benzothiophen-4-Ol within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:53.1 occ:1.00 F23 A:UY3401 0.0 53.1 1.0 C20 A:UY3401 1.4 52.5 1.0 C22 A:UY3401 2.3 52.3 1.0 C13 A:UY3401 2.3 51.9 1.0 H36 A:UY3401 2.6 52.3 0.0 H31 A:UY3401 2.6 51.9 0.0 OG A:SER246 3.2 37.8 1.0 ND2 A:ASN341 3.3 38.5 1.0 CZ A:PHE254 3.3 42.8 1.0 CE2 A:PHE254 3.4 43.1 1.0 C21 A:UY3401 3.6 52.1 1.0 C9 A:UY3401 3.6 51.5 1.0 CE2 A:PHE244 3.6 45.6 1.0 CG A:ASN341 3.7 39.3 1.0 CB A:SER246 3.7 36.3 1.0 OD1 A:ASN341 3.8 40.0 1.0 NE2 A:HIS248 3.9 41.0 1.0 CZ A:PHE244 4.0 45.5 1.0 C14 A:UY3401 4.1 51.6 1.0 CE1 A:HIS248 4.5 41.2 1.0 CE1 A:PHE254 4.5 42.9 1.0 CD2 A:PHE254 4.6 42.7 1.0 F24 A:UY3401 4.7 52.5 1.0 CB A:ASN341 4.7 38.6 1.0 CD2 A:PHE244 4.8 44.9 1.0 C4 A:UY3401 4.8 51.5 1.0 H25 A:UY3401 4.9 50.5 0.0 H26 A:UY3401 5.0 50.5 0.0

Fluorine binding site 4 out of 4 in the Structure of HIF2A-Arnt Heterodimer in Complex with (4S)-1-(3,5- Difluorophenyl)-5,5-Difluoro-3-Methanesulfonyl-4,5,6,7-Tetrahydro-2- Benzothiophen-4-Ol


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Structure of HIF2A-Arnt Heterodimer in Complex with (4S)-1-(3,5- Difluorophenyl)-5,5-Difluoro-3-Methanesulfonyl-4,5,6,7-Tetrahydro-2- Benzothiophen-4-Ol within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:52.5 occ:1.00 F24 A:UY3401 0.0 52.5 1.0 C21 A:UY3401 1.4 52.1 1.0 C22 A:UY3401 2.3 52.3 1.0 C14 A:UY3401 2.3 51.6 1.0 H32 A:UY3401 2.6 51.6 0.0 H36 A:UY3401 2.6 52.3 0.0 SD A:MET309 3.2 52.4 1.0 CG A:MET309 3.2 47.4 1.0 CE A:MET309 3.4 47.2 1.0 C20 A:UY3401 3.6 52.5 1.0 C9 A:UY3401 3.6 51.5 1.0 CE2 A:TYR307 3.6 46.9 1.0 CB A:MET309 3.7 45.1 1.0 CE1 A:TYR281 3.8 52.0 1.0 OH A:TYR307 4.1 48.3 1.0 C13 A:UY3401 4.1 51.9 1.0 CD1 A:TYR281 4.2 51.4 1.0 CD1 A:LEU319 4.2 52.0 1.0 CZ A:TYR307 4.3 47.4 1.0 CB A:PHE280 4.6 50.1 1.0 O A:ALA277 4.6 46.4 1.0 CD2 A:TYR307 4.6 46.1 1.0 F23 A:UY3401 4.7 53.1 1.0 CA A:MET309 4.7 44.4 1.0 C4 A:UY3401 4.8 51.5 1.0 CB A:ALA277 4.9 46.9 1.0 CZ A:TYR281 4.9 52.4 1.0

H.P.Buchstaller, A.Sala-Hojman, M.Leiendecker, J.Albers, U.Anlauf, N.Berges, L.Dong, T.Fuchss, M.Germann, T.Knehans, M.Krier, M.Lecomte, D.Muller, S.R.Muller, B.Leuthner, R.Lindemann, D.Musil, M.Nowak, V.Reither, C.Rettig, C.E.M.Schindler, U.Pakulska, D.Spuck, A.Wegener, A.Zarebski. Discovery of Cycloalkyl[ C ]Thiophenes As Novel Scaffolds For Hypoxia-Inducible Factor-2 Alpha Inhibitors. J.Med.Chem. 2023.
ISSN: ISSN 0022-2623
PubMed: 37403966
DOI: 10.1021/ACS.JMEDCHEM.3C00332