NRX-103094 is a potent enhancer of the interaction between β-catenin and the homologous E3 ligase SCFβ-TrCP, increasing the affinity of pSer33/Ser37 β-catenin for β-TrCP with an EC50 of 62 nM and a Kd of 0.6 nM.

β-catenin-β-TrCP:0.6 nM(Kd), β-catenin-β-TrCP:62 nM(EC50)

RX-103094 demonstrates high potency against the pSer33/Ser37 β-catenin peptide with an EC50 of 457 nM. At 250 nM, NRX-103094 enhances the ubiquitylation of the pSer33/S37A β-catenin peptide to levels surpassing those of the wild-type pSer33/pSer37.[1]
NRX-103094 significantly enhances the binding affinity of the S33E/S37A phosphomimetic peptide for β-TrCP, reducing it from >5 μM in the absence of the compound to 22 nM in the presence of 40 μM NRX-103094. In the presence of 20 μM NRX-103094, we observe robust, time-dependent ubiquitylation of the S33E/S37A β-catenin peptide. Similarly, when 20 μM NRX-103094 is present, the full-length S33E/S37A β-catenin protein undergoes strong ubiquitylation, with ubiquitylation levels approaching those of the WT full-length β-catenin protein.[1]