NRX-252114

• CAT Number: I045620
• CAS Number: 2763260-39-3
• Molecular Formula: C22H12Cl2F3N3O2S
• Molecular Weight: 510.32
• Purity: ≥95%
• Synonyms: 2-[4-(2,6-dichlorophenyl)sulfanyl-2-oxo-6-(trifluoromethyl)-1H-pyridine-3-carbonyl]-1,3-dihydroisoindole-4-carbonitrile
• InChI: InChI=1S/C22H12Cl2F3N3O2S/c23-14-5-2-6-15(24)19(14)33-16-7-17(22(25,26)27)29-20(31)18(16)21(32)30-9-12-4-1-3-11(8-28)13(12)10-30/h1-7H,9-10H2,(H,29,31)
• InChIKey: BMQXGPBUQGPLOV-UHFFFAOYSA-N
• SMILES: C1C2=C(CN1C(=O)C3=C(C=C(NC3=O)C(F)(F)F)SC4=C(C=CC=C4Cl)Cl)C(=CC=C2)C#N

NRX-252114 is a potent enhancer of the interaction between β-catenin, and its cognate E3 ligase, SCFβ-TrCP. NRX-252114 enhances the binding of pSer33/S37A β-catenin peptide for β-TrCP with an EC50 of 6.5 nM and a Kd of 0.4 nM. NRX-252114 induces mutant β-catenin degradation[1].
NRX-252114 (20 μM) enhances the binding of pSer33/S37A β-catenin peptide for β-TrCP, with more than 1500-fold co-operativity[1].
NRX-252114 (0-25 μM) increases the ubiquitylation of pSer33/S37A β-catenin peptide to form long ubiquitin chains[1].
NRX-252114 (0-25 μM) enhances the ubiquitylation of S33E/S37A β-catenin protein, as well as unphosphorylated Ser33/S37A β-catenin peptides[1].
NRX-252114 (20 μM, 6 h) results in robust S33E/S37A β-catenin:β-TrCP interaction in the transfected HEK293T cells[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]