compound 41 [PMID: 36630177]   Click here for help

GtoPdb Ligand ID: 12331

Compound class: Synthetic organic
Comment: This compound is reported to disrupt the β-catenin/B-cell lymphoma 9 (BCL9) interaction, by binding to β-catenin [1]. It was designed to block Wnt signalling and expression of oncogenic Wnt target genes, as a mechanism to target colorectal cancer. Since approximately 80% of colorectal cancers carry activating Wnt/β-catenin pathway mutations, this pathway is an active molecular target for oncology therapeutic development.
The chemical structure shown here is used to represent the racemic mixture of (S)-41 and (R)-41. Experiments comparing the in vitro activities of the isolated enantiomers and the racemate, showed that the chiral centers in the molecule do not significantly alter its binding interaction with β-catenin [1].
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 12
Topological polar surface area 126.61
Molecular weight 728.22
XLogP 8.39
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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Canonical SMILES CC(c1ccc(cc1)c1cccc(c1)S(=O)(=O)N1CCCC(C1)c1cccc(c1)OC(C(=O)NS(=O)(=O)c1ccc(cc1)C(F)(F)F)(C)C)C
Isomeric SMILES C(C)(C)c1ccc(cc1)c1cc(ccc1)S(=O)(=O)N1CC(CCC1)c1cc(OC(C(=O)NS(=O)(=O)c2ccc(cc2)C(F)(F)F)(C)C)ccc1
InChI InChI=1S/C37H39F3N2O6S2/c1-25(2)26-13-15-27(16-14-26)29-9-6-12-34(23-29)50(46,47)42-21-7-10-30(24-42)28-8-5-11-32(22-28)48-36(3,4)35(43)41-49(44,45)33-19-17-31(18-20-33)37(38,39)40/h5-6,8-9,11-20,22-23,25,30H,7,10,21,24H2,1-4H3,(H,41,43)
InChI Key QQIAMXDPJRMMQZ-UHFFFAOYSA-N
Selectivity at ligand targets
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
β-catenin Hs None Binding 6.6 pKd - 1
pKd 6.6 (Kd 2.6x10-7 M) [1]
Description: Binding affinity for β-catenin determined by SPR assay