Structure of PDB 5tbm Chain A Binding Site BS01

Receptor Information

>5tbm Chain A (length=106) Species: 9606 (Homo sapiens)

LDSKTFLSEHSMDMKFTYCDDRITELIGYHPEELLGRSAYEFYHALDSEN
MTKSHQNLCTKGQVVSGQYRMLAKHGGYVWLETQGTVIYNPPQCIMCVNY
VLSEIE

Ligand information

• Ligand ID: 79A
• InChI: InChI=1S/C17H12F3NO4S/c1-26(23,24)14-3-2-13(12-7-17(19,20)16(22)15(12)14)25-11-5-9(8-21)4-10(18)6-11/h2-6,16,22H,7H2,1H3/t16-/m0/s1
• InChIKey: ONBSHRSJOPSEGS-INIZCTEOSA-N
• SMILES:
  CACTVS 3.385: C[S](=O)(=O)c1ccc(Oc2cc(F)cc(c2)C#N)c3CC(F)(F)[C@@H](O)c13
  CACTVS 3.385: C[S](=O)(=O)c1ccc(Oc2cc(F)cc(c2)C#N)c3CC(F)(F)[CH](O)c13
  OpenEye OEToolkits 2.0.6: CS(=O)(=O)c1ccc(c2c1[C@@H](C(C2)(F)F)O)Oc3cc(cc(c3)F)C#N
  OpenEye OEToolkits 2.0.6: CS(=O)(=O)c1ccc(c2c1C(C(C2)(F)F)O)Oc3cc(cc(c3)F)C#N
  ACDLabs 12.01: N#Cc1cc(cc(c1)F)Oc2ccc(c3c2CC(C3O)(F)F)S(C)(=O)=O
• Formula: C17 H12 F3 N O4 S
• Name: 3-{[(1S)-2,2-difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl]oxy}-5-fluorobenzonitrile;
  PT2385
• ChEMBL: CHEMBL4173075
• DrugBank: DB16055
• ZINC: ZINC000230453533
• PDB chain: 5tbm Chain A Residue 401

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5tbm A Small-Molecule Antagonist of HIF2 alpha Is Efficacious in Preclinical Models of Renal Cell Carcinoma.
• Resolution: 1.85 Å
• Binding residue (original residue number in PDB): F244 H248 M252 A277 Y281 H293 L296 V302 Y307 M309 T321 I337 C339 N341
• Binding residue (residue number reindexed from 1): F6 H10 M14 A39 Y43 H55 L58 V64 Y69 M71 T83 I95 C97 N99
• Annotation score: 1
• Binding affinity: MOAD: Kd=0.049uM
  PDBbind-CN: -logKd/Ki=7.31,Kd=0.049uM
  BindingDB: EC50=27nM,IC50=12nM

External links

• PDB: RCSB:5tbm, PDBe:5tbm, PDBj:5tbm
• PDBsum: 5tbm
• PubMed: 27635045
• UniProt: Q99814|EPAS1_HUMAN Endothelial PAS domain-containing protein 1 (Gene Name=EPAS1)