Structure of PDB 5t97 Chain A Binding Site BS01

Receptor Information

>5t97 Chain A (length=177) Species: 9606 (Homo sapiens)

LTADQMVSALLDAEPPILYMGLLTNLADRELVHMINWAKRVPGFVDLTLH
DQVHLLESAWLEILMIGLVWRSMEHPGKLLFAPNLLLGMVEIFDMLLATS
SRFRMMNLQGEEFVCLKSIILLNSGHIHRVLDKITDTLIHLMAKAGLTLQ
QQHQRLAQLLLILSHIRHMSNKGMEHL

Ligand information

• Ligand ID: 782
• InChI: InChI=1S/C28H29NO3/c1-19(2)21-7-11-24(12-8-21)29-17-16-22-18-25(30)13-14-26(22)28(29,3)23-9-4-20(5-10-23)6-15-27(31)32/h4-15,18-19,30H,16-17H2,1-3H3,(H,31,32)/b15-6+/t28-/m1/s1
• InChIKey: HKXVKUOGCLJVEZ-AJVPWASQSA-N
• SMILES:
  OpenEye OEToolkits 2.0.6: CC(C)c1ccc(cc1)N2CCc3cc(ccc3[C@@]2(C)c4ccc(cc4)/C=C/C(=O)O)O
  CACTVS 3.385: CC(C)c1ccc(cc1)N2CCc3cc(O)ccc3[C@@]2(C)c4ccc(/C=C/C(O)=O)cc4
  ACDLabs 12.01: c3c(cc2CCN(C(c1ccc(cc1)[C@H]=[C@H]C(=O)O)(C)c2c3)c4ccc(cc4)C(C)C)O
  CACTVS 3.385: CC(C)c1ccc(cc1)N2CCc3cc(O)ccc3[C]2(C)c4ccc(C=CC(O)=O)cc4
  OpenEye OEToolkits 2.0.6: CC(C)c1ccc(cc1)N2CCc3cc(ccc3C2(C)c4ccc(cc4)C=CC(=O)O)O
• Formula: C28 H29 N O3
• Name: (2E)-3-(4-{(1R)-6-hydroxy-1-methyl-2-[4-(propan-2-yl)phenyl]-1,2,3,4-tetrahydroisoquinolin-1-yl}phenyl)prop-2-enoic acid
• ChEMBL: CHEMBL4063838
• PDB chain: 5t97 Chain A Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5t97 Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ER alpha + Breast Cancer.
• Resolution: 3.0 Å
• Binding residue (original residue number in PDB): T347 A350 D351 E353 M388 F404 M421 I424 H524
• Binding residue (residue number reindexed from 1): T24 A27 D28 E30 M65 F81 M89 I92 H176
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=7.77,IC50=17nM
  BindingDB: IC50=34nM

External links

• PDB: RCSB:5t97, PDBe:5t97, PDBj:5t97
• PDBsum: 5t97
• PubMed: 28296398
• UniProt: P03372|ESR1_HUMAN Estrogen receptor (Gene Name=ESR1)