NRX-103094 is a potent enhancer of the interaction between β-catenin, and its cognate E3 ligase, SCF^β-TrCP. NRX-103094 enhances the binding of pSer33/Ser37 β-catenin peptide for β-TrCP with an EC₅₀ of 62 nM and a K_d of 0.6 nM.

NRX-103094 shows high potency with pSer33/Ser37 β-catenin peptide (EC₅₀ of 457 nM). NRX-103094 potentiates the ubiquitylation of pSer33/S37A β-catenin peptide to levels greater than wild-type pSer33/pSer37 levels at 250 nM.
NRX-103094 enhances the S33E/S37A phosphomimetic peptide binding affinity for β-TrCP from >5 μM in the absence of compound to 22 nM in the presence of 40 μM compound. In the presence of 20 μM NRX-103094, robust time-dependent ubiquitylation of S33E/S37A β-catenin peptide is observed. Likewise, the full-length S33E/S37A β-catenin protein is strongly ubiquitylated in the presence of 20 μM NRX-103094, with the ubiquitylation levels approaching that of WT full-length β-catenin protein.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . Kyle R Simonetta, et al. Prospective discovery of small molecule enhancers of an E3 ligase-substrate interaction. Nat Commun. 2019 Mar 29;10(1):1402.  [Content Brief]