Structure of PDB 6pfm Chain A Binding Site BS01

Receptor Information

>6pfm Chain A (length=224) Species: 9606 (Homo sapiens)

ALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVH
MINWAKRVPGFVDLTSHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAP
NLLLDRNQGKCVEGMVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNS
GVYTFLSSTLKSLEEKDHIHRVLDKITDTLIHLMAKAGLTLQQQHQRLAQ
LLLILSHIRHMSNKGMEHLYSMKC

Ligand information

• Ligand ID: OGJ
• InChI: InChI=1S/C28H28FNO4/c1-18-25-14-23(32)7-10-26(25)34-28(27(18)21-3-2-4-22(31)13-21)20-5-8-24(9-6-20)33-12-11-30-16-19(15-29)17-30/h2-10,13-14,19,28,31-32H,11-12,15-17H2,1H3/t28-/m0/s1
• InChIKey: KJAAPZIFCQQQKX-NDEPHWFRSA-N
• SMILES:
  CACTVS 3.385: CC1=C([CH](Oc2ccc(O)cc12)c3ccc(OCCN4CC(CF)C4)cc3)c5cccc(O)c5
  OpenEye OEToolkits 2.0.7: CC1=C([C@@H](Oc2c1cc(cc2)O)c3ccc(cc3)OCCN4CC(C4)CF)c5cccc(c5)O
  OpenEye OEToolkits 2.0.7: CC1=C(C(Oc2c1cc(cc2)O)c3ccc(cc3)OCCN4CC(C4)CF)c5cccc(c5)O
  ACDLabs 12.01: C4(c2ccc(OCCN1CC(C1)CF)cc2)Oc3ccc(cc3C(=C4c5cccc(c5)O)C)O
  CACTVS 3.385: CC1=C([C@@H](Oc2ccc(O)cc12)c3ccc(OCCN4CC(CF)C4)cc3)c5cccc(O)c5
• Formula: C28 H28 F N O4
• Name: (2S)-2-(4-{2-[3-(fluoromethyl)azetidin-1-yl]ethoxy}phenyl)-3-(3-hydroxyphenyl)-4-methyl-2H-1-benzopyran-6-ol
• ChEMBL: CHEMBL4447340
• DrugBank: DB14934
• PDB chain: 6pfm Chain A Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6pfm Discovery of a C-8 hydroxychromene as a potent degrader of estrogen receptor alpha with improved rat oral exposure over GDC-0927.
• Resolution: 2.84 Å
• Binding residue (original residue number in PDB): L346 A350 D351 L387 L391 F404 M421 G521 H524 L525
• Binding residue (residue number reindexed from 1): L40 A44 D45 L81 L85 F98 M115 G215 H218 L219
• Annotation score: 1
• Binding affinity: BindingDB: IC50=0.030000nM

External links

• PDB: RCSB:6pfm, PDBe:6pfm, PDBj:6pfm
• PDBsum: 6pfm
• PubMed: 31311734
• UniProt: P03372|ESR1_HUMAN Estrogen receptor (Gene Name=ESR1)