Davies, Thomas G. published the artcileMonoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein-Protein Interaction with High Cell Potency Identified by Fragment-Based Discovery, COA of Formula: C8H8BrN3O, the publication is Journal of Medicinal Chemistry (2016), 59(8), 3991-4006, database is CAplus and MEDLINE.
KEAP1 is the key regulator of the NRF2-mediated cytoprotective response, and increasingly recognized as a target for diseases involving oxidative stress. Pharmacol. intervention has focused on mols. that decrease NRF2-ubiquitination through covalent modification of KEAP1 cysteine residues, but such electrophilic compounds lack selectivity and may be associated with off-target toxicity. We report here the first use of a fragment-based approach to directly target the KEAP1 Kelch-NRF2 interaction. X-ray crystallog. screening identified three distinct “hot-spots” for fragment binding within the NRF2 binding pocket of KEAP1, allowing progression of a weak fragment hit to mols. with nanomolar affinity for KEAP1 while maintaining drug-like properties. This work resulted in a promising lead compound (I) which exhibits tight and selective binding to KEAP1, and activates the NRF2 antioxidant response in cellular and in vivo models, thereby providing a high quality chem. probe to explore the therapeutic potential of disrupting the KEAP1-NRF2 interaction.
Journal of Medicinal Chemistry published new progress about 1799973-82-2. 1799973-82-2 belongs to triazoles, auxiliary class Other Aromatic Heterocyclic,Bromide,Ether, name is 5-Bromo-7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazole, and the molecular formula is C8H8BrN3O, COA of Formula: C8H8BrN3O.
Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics