NRX-103094

• CAT Number: I045284
• CAS Number: 2763260-36-0
• Molecular Formula: C20H11Cl2F3N2O4S
• Molecular Weight: 503.28
• Purity: ≥95%
• Synonyms: 3-[[4-(2,6-dichlorophenyl)sulfanyl-2-oxo-6-(trifluoromethyl)-1H-pyridine-3-carbonyl]amino]benzoic acid
• InChI: InChI=1S/C20H11Cl2F3N2O4S/c21-11-5-2-6-12(22)16(11)32-13-8-14(20(23,24)25)27-18(29)15(13)17(28)26-10-4-1-3-9(7-10)19(30)31/h1-8H,(H,26,28)(H,27,29)(H,30,31)
• InChIKey: HFBGFWJURBVNFD-UHFFFAOYSA-N
• SMILES: C1=CC(=CC(=C1)NC(=O)C2=C(C=C(NC2=O)C(F)(F)F)SC3=C(C=CC=C3Cl)Cl)C(=O)O

NRX-103094 is a potent enhancer of the interaction between β-catenin, and its cognate E3 ligase, SCFβ-TrCP. NRX-103094 enhances the binding of pSer33/Ser37 β-catenin peptide for β-TrCP with an EC50 of 62 nM and a Kd of 0.6 nM[1].
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[1].
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[1].

Reference

[1]. 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]