Structure of PDB 6uwu Chain A Binding Site BS01

Receptor Information

>6uwu Chain A (length=126) Species: 9606 (Homo sapiens)

MNPPPPETSNPNKPKRQTNQLQYLLRVVLKTLWKHQFAWPFQQPVDAVKL
NLPDYYKIIKTPMDMGTIKKRLENNYYWNAQECIQDFNTMFTNCYIYNKP
GDDIVLMAEALEKLFLQKINELPTEE

Ligand information

• Ligand ID: QKP
• InChI: InChI=1S/C27H34N2O6/c1-17-10-19(23-14-22(31)26-24(33-5)12-21(32-4)13-25(26)35-23)11-18(2)27(17)34-16-20(30)15-29-8-6-28(3)7-9-29/h10-14,20,30H,6-9,15-16H2,1-5H3/t20-/m1/s1
• InChIKey: UDPXIEUTIPNLKC-HXUWFJFHSA-N
• SMILES:
  CACTVS 3.385: COc1cc(OC)c2C(=O)C=C(Oc2c1)c3cc(C)c(OC[CH](O)CN4CCN(C)CC4)c(C)c3
  ACDLabs 12.01: c2(OCC(CN1CCN(CC1)C)O)c(cc(cc2C)C3=CC(c4c(cc(cc4O3)OC)OC)=O)C
  OpenEye OEToolkits 2.0.7: Cc1cc(cc(c1OC[C@@H](CN2CCN(CC2)C)O)C)C3=CC(=O)c4c(cc(cc4OC)OC)O3
  CACTVS 3.385: COc1cc(OC)c2C(=O)C=C(Oc2c1)c3cc(C)c(OC[C@H](O)CN4CCN(C)CC4)c(C)c3
  OpenEye OEToolkits 2.0.7: Cc1cc(cc(c1OCC(CN2CCN(CC2)C)O)C)C3=CC(=O)c4c(cc(cc4OC)OC)O3
• Formula: C27 H34 N2 O6
• Name: 2-{4-[(2R)-2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy]-3,5-dimethylphenyl}-5,7-dimethoxy-4H-1-benzopyran-4-one
• ChEMBL: CHEMBL4557050
• PDB chain: 6uwu Chain A Residue 206

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6uwu Discovery of Orally Bioavailable Chromone Derivatives as Potent and Selective BRD4 Inhibitors: Scaffold Hopping, Optimization, and Pharmacological Evaluation.
• Resolution: 2.0 Å
• Binding residue (original residue number in PDB): P82 F83 V87 L92 L94 N140 I146
• Binding residue (residue number reindexed from 1): P40 F41 V45 L50 L52 N98 I104
• Annotation score: 1
• Binding affinity: MOAD: ic50~70nM
  BindingDB: Kd=718nM,IC50=280nM

External links

• PDB: RCSB:6uwu, PDBe:6uwu, PDBj:6uwu
• PDBsum: 6uwu
• PubMed: 32255647
• UniProt: O60885|BRD4_HUMAN Bromodomain-containing protein 4 (Gene Name=BRD4)