Fluorine in PDB 8ck3: Structure of HIF2A-Arnt Heterodimer in Complex with (S)-1-(3,5- Difluoro-Phenyl)-5,5-Difluoro-3-Methanesulfonyl-5,6-Dihydro-4H- Cyclopenta[C]Thiophen-4-Ol

The structure of Structure of HIF2A-Arnt Heterodimer in Complex with (S)-1-(3,5- Difluoro-Phenyl)-5,5-Difluoro-3-Methanesulfonyl-5,6-Dihydro-4H- Cyclopenta[C]Thiophen-4-Ol, PDB code: 8ck3 was solved by D.Musil, M.Lehmannn, L.Diehl, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	53.47 / 1.71
Space group	C 1 2 1
Cell size a, b, c (Å), α, β, γ (°)	72.671, 83.594, 40.935, 90, 106.86, 90
R / Rfree (%)	19.7 / 22.7

The binding sites of Fluorine atom in the Structure of HIF2A-Arnt Heterodimer in Complex with (S)-1-(3,5- Difluoro-Phenyl)-5,5-Difluoro-3-Methanesulfonyl-5,6-Dihydro-4H- Cyclopenta[C]Thiophen-4-Ol (pdb code 8ck3). 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 (S)-1-(3,5- Difluoro-Phenyl)-5,5-Difluoro-3-Methanesulfonyl-5,6-Dihydro-4H- Cyclopenta[C]Thiophen-4-Ol, PDB code: 8ck3:
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 (S)-1-(3,5- Difluoro-Phenyl)-5,5-Difluoro-3-Methanesulfonyl-5,6-Dihydro-4H- Cyclopenta[C]Thiophen-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 (S)-1-(3,5- Difluoro-Phenyl)-5,5-Difluoro-3-Methanesulfonyl-5,6-Dihydro-4H- Cyclopenta[C]Thiophen-4-Ol within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:36.5 occ:1.00 F6 A:UXU401 0.0 36.5 1.0 C2 A:UXU401 1.4 38.3 1.0 F7 A:UXU401 2.1 38.8 1.0 C1 A:UXU401 2.4 39.5 1.0 C5 A:UXU401 2.4 38.7 1.0 H27 A:UXU401 2.7 38.7 0.0 O4 A:UXU401 2.7 39.7 1.0 H24 A:UXU401 2.9 39.5 0.0 H26 A:UXU401 2.9 38.7 0.0 CA A:MET252 3.2 26.7 1.0 CG A:MET252 3.2 32.6 1.0 CB A:MET252 3.5 28.8 1.0 C3 A:UXU401 3.5 40.2 1.0 C9 A:UXU401 3.6 39.8 1.0 H25 A:UXU401 3.7 39.7 0.0 CD1 A:ILE337 3.7 23.8 1.0 CE1 A:HIS293 3.7 42.1 1.0 ND1 A:HIS293 3.8 42.2 1.0 CB A:HIS248 3.9 18.9 1.0 N A:MET252 4.0 27.5 1.0 CG A:HIS248 4.1 20.8 1.0 C A:MET252 4.2 24.6 1.0 O A:MET252 4.3 24.5 1.0 ND1 A:HIS248 4.3 21.3 1.0 O A:SER249 4.5 24.6 1.0 CD2 A:HIS248 4.6 22.0 1.0 CG2 A:ILE337 4.7 23.1 1.0 NE2 A:HIS293 4.7 42.1 1.0 SD A:MET252 4.8 42.3 1.0 CB A:ILE337 4.8 23.0 1.0 CG1 A:ILE337 4.8 22.5 1.0 C8 A:UXU401 4.9 41.8 1.0 C12 A:UXU401 4.9 40.5 1.0 CG A:HIS293 4.9 40.4 1.0 CE1 A:HIS248 5.0 21.8 1.0

Fluorine binding site 2 out of 4 in the Structure of HIF2A-Arnt Heterodimer in Complex with (S)-1-(3,5- Difluoro-Phenyl)-5,5-Difluoro-3-Methanesulfonyl-5,6-Dihydro-4H- Cyclopenta[C]Thiophen-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 (S)-1-(3,5- Difluoro-Phenyl)-5,5-Difluoro-3-Methanesulfonyl-5,6-Dihydro-4H- Cyclopenta[C]Thiophen-4-Ol within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:38.8 occ:1.00 F7 A:UXU401 0.0 38.8 1.0 C2 A:UXU401 1.4 38.3 1.0 F6 A:UXU401 2.1 36.5 1.0 C1 A:UXU401 2.4 39.5 1.0 C5 A:UXU401 2.4 38.7 1.0 H24 A:UXU401 2.4 39.5 0.0 H26 A:UXU401 2.5 38.7 0.0 C9 A:UXU401 3.0 39.8 1.0 C3 A:UXU401 3.0 40.2 1.0 CG2 A:ILE337 3.2 23.1 1.0 H27 A:UXU401 3.3 38.7 0.0 CG A:HIS248 3.3 20.8 1.0 CD2 A:HIS248 3.3 22.0 1.0 SG A:CYS339 3.4 26.1 1.0 CB A:HIS248 3.5 18.9 1.0 O4 A:UXU401 3.6 39.7 1.0 CB A:ILE337 3.7 23.0 1.0 CD1 A:ILE337 3.8 23.8 1.0 NE2 A:HIS248 4.0 22.9 1.0 ND1 A:HIS248 4.0 21.3 1.0 H30 A:UXU401 4.2 43.9 0.0 H25 A:UXU401 4.2 39.7 0.0 C8 A:UXU401 4.3 41.8 1.0 C12 A:UXU401 4.3 40.5 1.0 CG1 A:ILE337 4.3 22.5 1.0 CE1 A:HIS248 4.4 21.8 1.0 H28 A:UXU401 4.5 43.9 0.0 C15 A:UXU401 4.8 43.9 1.0 CD2 A:LEU296 4.8 44.2 1.0 H32 A:UXU401 4.8 42.2 0.0 CA A:MET252 4.8 26.7 1.0 CA A:HIS248 4.9 19.1 1.0 O A:ILE337 4.9 22.1 1.0

Fluorine binding site 3 out of 4 in the Structure of HIF2A-Arnt Heterodimer in Complex with (S)-1-(3,5- Difluoro-Phenyl)-5,5-Difluoro-3-Methanesulfonyl-5,6-Dihydro-4H- Cyclopenta[C]Thiophen-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 (S)-1-(3,5- Difluoro-Phenyl)-5,5-Difluoro-3-Methanesulfonyl-5,6-Dihydro-4H- Cyclopenta[C]Thiophen-4-Ol within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:44.2 occ:1.00 F22 A:UXU401 0.0 44.2 1.0 C19 A:UXU401 1.4 43.5 1.0 C17 A:UXU401 2.3 42.5 1.0 C21 A:UXU401 2.3 43.2 1.0 H31 A:UXU401 2.6 42.5 0.0 H33 A:UXU401 2.6 43.2 0.0 SD A:MET309 3.3 31.5 1.0 CG A:MET309 3.5 29.2 1.0 CE1 A:TYR281 3.5 33.3 1.0 C20 A:UXU401 3.6 43.0 1.0 C16 A:UXU401 3.6 41.6 1.0 CE2 A:TYR307 3.7 28.4 1.0 CE A:MET309 3.7 28.8 1.0 CB A:MET309 3.8 27.7 1.0 OH A:TYR307 3.9 29.9 1.0 CD1 A:TYR281 4.0 31.8 1.0 C18 A:UXU401 4.1 42.2 1.0 CZ A:TYR307 4.3 29.2 1.0 CB A:PHE280 4.3 25.0 1.0 O A:ALA277 4.4 25.4 1.0 CZ A:TYR281 4.5 33.9 1.0 F23 A:UXU401 4.7 43.7 1.0 CD2 A:TYR307 4.7 27.9 1.0 CA A:MET309 4.7 28.1 1.0 OH A:TYR281 4.8 35.5 1.0 CB A:ALA277 4.8 25.0 1.0 CD2 A:LEU319 4.8 30.7 1.0 C12 A:UXU401 4.8 40.5 1.0

Fluorine binding site 4 out of 4 in the Structure of HIF2A-Arnt Heterodimer in Complex with (S)-1-(3,5- Difluoro-Phenyl)-5,5-Difluoro-3-Methanesulfonyl-5,6-Dihydro-4H- Cyclopenta[C]Thiophen-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 (S)-1-(3,5- Difluoro-Phenyl)-5,5-Difluoro-3-Methanesulfonyl-5,6-Dihydro-4H- Cyclopenta[C]Thiophen-4-Ol within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:43.7 occ:1.00 F23 A:UXU401 0.0 43.7 1.0 C20 A:UXU401 1.4 43.0 1.0 C21 A:UXU401 2.3 43.2 1.0 C18 A:UXU401 2.3 42.2 1.0 H32 A:UXU401 2.6 42.2 0.0 H33 A:UXU401 2.6 43.2 0.0 OG A:SER246 3.0 17.2 1.0 ND2 A:ASN341 3.3 20.6 1.0 CE2 A:PHE254 3.4 23.1 1.0 CB A:SER246 3.5 17.9 1.0 CE2 A:PHE244 3.5 21.5 1.0 CZ A:PHE254 3.5 22.5 1.0 C19 A:UXU401 3.6 43.5 1.0 C16 A:UXU401 3.6 41.6 1.0 CG A:ASN341 3.7 20.2 1.0 OD1 A:ASN341 3.7 20.7 1.0 NE2 A:HIS248 3.9 22.9 1.0 CZ A:PHE244 3.9 21.2 1.0 C17 A:UXU401 4.1 42.5 1.0 CE1 A:HIS248 4.2 21.8 1.0 CD2 A:PHE254 4.6 22.4 1.0 CD2 A:PHE244 4.6 20.6 1.0 F22 A:UXU401 4.7 44.2 1.0 CB A:ASN341 4.7 18.4 1.0 CE1 A:PHE254 4.8 22.2 1.0 C12 A:UXU401 4.8 40.5 1.0 CA A:SER246 4.9 18.9 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