NRX-103094

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.

Product information

Molecular Weight: 503.28

Formula: C20H11Cl2F3N2O4S

Chemical Name: 3-{4-[(2,6-dichlorophenyl)sulfanyl]-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridine-3-amido}benzoic acid

Smiles: OC(=O)C1C=C(C=CC=1)NC(=O)C1=C(C=C(NC1=O)C(F)(F)F)SC1C(Cl)=CC=CC=1Cl

InChiKey: HFBGFWJURBVNFD-UHFFFAOYSA-N

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)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: To be determined

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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.

References:

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.

Products are for research use only. Not for human use.