1H-Isoindole-4-carbonitrile, 2-[[4-[(2,6-dichlorophenyl)thio]-1,2-dihydro-2-oxo-6-(trifluoromethyl)-3-pyridinyl]carbonyl]-2,3-dihydro-

Description

NRX-252114 is a potent enhancer of the interaction between β-catenin, and its cognate E3 ligase, SCF^β-TrCP. NRX-252114 enhances the binding of pSer33/S37A β-catenin peptide for β-TrCP with an EC₅₀ of 6.5 nM and a K_d of 0.4 nM. NRX-252114 induces mutant β-catenin degradation^[1].

NRX-252114 enhances the binding of pSer33/S37A β-catenin peptide for β-TrCP with >1500-fold cooperativity, surpassing the affinity of wild-type doubly-phosphorylated peptide. NRX-252114 further enhances the ubiquitylation of pSer33/S37A β-catenin peptide to form long ubiquitin chains^[1].
The non-phosphorylated Ser33/Ser37 peptide binds β-TrCP with very weak affinity (>100 μM); however, in the presence of 20 μM NRX-252114 that binding affinity is enhanced to 180 nM. NRX-252114 also potentiates the ubiquitylation of unphosphorylated Ser33/S37A β-catenin peptides by the SCFβ-TrCP complex^[1].