Structure of PDB 5t92 Chain A Binding Site BS01

Receptor Information

>5t92 Chain A (length=183) Species: 9606 (Homo sapiens)

LTADQMVSALLDAEPPILYSSEASMMGLLTNLADRELVHMINWAKRVPGF
VDLTLHDQVHLLESAWLEILMIGLVWRSMEHPGKLLFAPNLLLGMVEIFD
MLLATSSRFRMMNLQGEEFVCLKSIILLNSGHIHRVLDKITDTLIHLMAK
AGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHL

Ligand information

• Ligand ID: 77W
• InChI: InChI=1S/C25H22FNO3/c1-25(19-5-2-17(3-6-19)4-13-24(29)30)23-12-11-22(28)16-18(23)14-15-27(25)21-9-7-20(26)8-10-21/h2-13,16,28H,14-15H2,1H3,(H,29,30)/b13-4+/t25-/m1/s1
• InChIKey: NZVCGXAIFBXHCL-UITUQSNXSA-N
• SMILES:
  OpenEye OEToolkits 2.0.6: C[C@]1(c2ccc(cc2CCN1c3ccc(cc3)F)O)c4ccc(cc4)/C=C/C(=O)O
  CACTVS 3.385: C[C@@]1(N(CCc2cc(O)ccc12)c3ccc(F)cc3)c4ccc(/C=C/C(O)=O)cc4
  ACDLabs 12.01: c4c(cc3CCN(c1ccc(cc1)F)C(C)(c2ccc(cc2)[C@H]=[C@H]C(O)=O)c3c4)O
  OpenEye OEToolkits 2.0.6: CC1(c2ccc(cc2CCN1c3ccc(cc3)F)O)c4ccc(cc4)C=CC(=O)O
  CACTVS 3.385: C[C]1(N(CCc2cc(O)ccc12)c3ccc(F)cc3)c4ccc(C=CC(O)=O)cc4
• Formula: C25 H22 F N O3
• Name: (2E)-3-{4-[(1R)-2-(4-fluorophenyl)-6-hydroxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl]phenyl}prop-2-enoic acid
• PDB chain: 5t92 Chain A Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5t92 Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ER alpha + Breast Cancer.
• Resolution: 2.22 Å
• Binding residue (original residue number in PDB): T347 A350 E353 L384 L387 M388 M421 I424 H524
• Binding residue (residue number reindexed from 1): T30 A33 E36 L67 L70 M71 M95 I98 H182
• Annotation score: 1
• Binding affinity: MOAD: ic50=16nM
  PDBbind-CN: -logKd/Ki=7.80,IC50=16nM

External links

• PDB: RCSB:5t92, PDBe:5t92, PDBj:5t92
• PDBsum: 5t92
• PubMed: 28296398
• UniProt: P03372|ESR1_HUMAN Estrogen receptor (Gene Name=ESR1)