NRX-2663

• CAT Number: I045285
• CAS Number: 2763260-34-8
• Molecular Formula: C20H13F3N2O5
• Molecular Weight: 418.32
• Purity: ≥95%
• Synonyms: 3-[[2-oxo-4-phenoxy-6-(trifluoromethyl)-1H-pyridine-3-carbonyl]amino]benzoic acid
• InChI: InChI=1S/C20H13F3N2O5/c21-20(22,23)15-10-14(30-13-7-2-1-3-8-13)16(18(27)25-15)17(26)24-12-6-4-5-11(9-12)19(28)29/h1-10H,(H,24,26)(H,25,27)(H,28,29)
• InChIKey: QMARDTCIJVODCK-UHFFFAOYSA-N
• SMILES: C1=CC=C(C=C1)OC2=C(C(=O)NC(=C2)C(F)(F)F)C(=O)NC3=CC=CC(=C3)C(=O)O

NRX-2663 is an enhancer of the interaction between β-catenin, and its cognate E3 ligase, SCFβ-TrCP. NRX-2663 enhances the binding of β-catenin peptide for β-TrCP with an EC50 of 22.9 µM and a Kd of 54.8 nM[1].
NRX-2663 displays both improved potency in the binding assay with pSer33/Ser37 β-catenin (EC50 of 80 µM) and cooperativity of binding (13-fold). NRX-2663 also markedly enhances the ubiquitylation of the pSer33/Ser37 β-catenin peptide, with ubiquitin chain formation at ligand concentrations of 16 μM and above resembling ubiquitin chain formation on wild-type pSer33/pSer37 β-catenin peptide[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]