1567836-15-0

Basic information

• Product Name: 2,2′-(naphthalene-1,4-diylbis(((4-methoxyphenyl)sulfonyl)azanediyl))diacetic acid
• Synonyms: 2,2′-(naphthalene-1,4-diylbis(((4-methoxyphenyl)sulfonyl)azanediyl))diacetic acid
• CAS NO: 1567836-15-0
• Molecular Weight: 614.654
• Mol File: 1567836-15-0.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: 2,2′-(naphthalene-1,4-diylbis(((4-methoxyphenyl)sulfonyl)azanediyl))diacetic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2,2′-(naphthalene-1,4-diylbis(((4-methoxyphenyl)sulfonyl)azanediyl))diacetic acid(1567836-15-0)
• EPA Substance Registry System: 2,2′-(naphthalene-1,4-diylbis(((4-methoxyphenyl)sulfonyl)azanediyl))diacetic acid(1567836-15-0)

Safety Data

• Hazardous Substances Data: 1567836-15-0(Hazardous Substances Data)

Upstream product

• 321694-20-6 4-methoxy-N-[4-[(4-methoxyphenyl)sulfonylamino]-1-naphthyl]benzenesulfonamide 
• 86-57-7 1-Nitronaphthalene 
• 1567836-16-1 diethyl 2,2′-(naphthalene-1,4-diylbis(((4-methoxyphenyl)sulfonyl)azanediyl))diacetate 
• 776-34-1 1-amino-4-nitronaphthalene 
• 2243-61-0 1,4-diaminonaphthalene 

Relevant articles and documents

A hydrogen peroxide responsive prodrug of Keap1-Nrf2 inhibitor for improving oral absorption and selective activation in inflammatory conditions

Transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) and its negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (Keap1), control the redox and metabolic homeostasis and oxidative stress. Inhibitors of Keap1-Nrf2 interaction are promising in oxidative stress related inflammatory diseases but now hit hurdles. By utilizing thiazolidinone moiety to shield the key carboxyl pharmacophore in Keap1-Nrf2 inhibitor, a hydrogen peroxide (H2O2)-responsive prodrug pro2 was developed. The prodrug modification improved the physicochemical properties and cell membrane permeability of the parent drug. Pro2 was stable and stayed inactive under various physiological conditions, while became active by stimulation of H2O2 or inflammation derived reactive oxygen species. Moreover, pro2 exhibited proper pharmacokinetic profile suitable for oral administration and enhanced anti-inflammatory efficiency in vivo. Thus, this novel prodrug approach may not only provide an important advance in the therapy of chronic inflammatory diseases with high level of H2O2, but also offer a fresh solution to improve the drug-like and selectivity issues of Keap1-Nrf2 inhibitors.

A Comparative Assessment Study of Known Small-Molecule Keap1-Nrf2 Protein-Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity

Inhibiting the protein-protein interaction (PPI) between the transcription factor Nrf2 and its repressor protein Keap1 has emerged as a promising strategy to target oxidative stress in diseases, including central nervous system (CNS) disorders. Numerous non-covalent small-molecule Keap1-Nrf2 PPI inhibitors have been reported to date, but many feature suboptimal physicochemical properties for permeating the blood-brain barrier, while others contain problematic structural moieties. Here, we present the first side-by-side assessment of all reported Keap1-Nrf2 PPI inhibitor classes using fluorescence polarization, thermal shift assay, and surface plasmon resonance - and further evaluate the compounds in an NQO1 induction cell assay and in counter tests for nonspecific activities. Surprisingly, half of the compounds were inactive or deviated substantially from reported activities, while we confirm the cross-assay activities for others. Through this study, we have identified the most promising Keap1-Nrf2 inhibitors that can serve as pharmacological probes or starting points for developing CNS-active Keap1 inhibitors.

Discovery of potent Keap1-Nrf2 protein-protein interaction inhibitor based on molecular binding determinants analysis

Keap1 is known to mediate the ubiquitination of Nrf2, a master regulator of the antioxidant response. Directly interrupting the Keap1-Nrf2 interaction has been emerged as a promising strategy to develop novel class of antioxidant, antiinflammatory, and anticancer agents. On the basis of the molecular binding determinants analysis of Keap1, we successfully designed and characterized the most potent protein-protein interaction (PPI) inhibitor of Keap1-Nrf2, compound 2, with KD value of 3.59 nM binding to Keap1 for the first time to single-digit nanomolar. Compound 2 can effectively disrupt the Nrf2-Keap1 interaction with an EC50 of 28.6 nM in the fluorescence polarization assay. It can also activate the Nrf2 transcription activity in the cell-based ARE-luciferase reporter assay in a dose-dependent manner. The qRT-PCR results of Nrf2 transcription targets gave the consistent results. These results confirm direct and highly efficient interruption of the Keap1-Nrf2 PPI can be fully achieved by small molecules.