Ontoria, Jesus M. published the artcileCombined Peptide and Small-Molecule Approach toward Nonacidic THIQ Inhibitors of the KEAP1/NRF2 Interaction, Product Details of C10H16O2, the publication is ACS Medicinal Chemistry Letters (2020), 11(5), 740-746, database is CAplus and MEDLINE.
The NRF2-ARE pathway is an intrinsic mechanism of defense against oxidative stress. Inhibition of the interaction between NRF2 and its main neg. regulator KEAP1 is an attractive strategy toward neuroprotective agents. We report here the identification of nonacidic tetrahydroisoquinolines (THIQs) that inhibit the KEAP1/NRF2 protein-protein interaction. Peptide SAR at one residue is utilized as a tool to probe structural changes within a specific pocket of the KEAP1 binding site. We used structural information from peptide screening at the P2 pocket, noncovalent small-mols. inhibitors, and the outcome from an explorative SAR at position 5 of THIQs to identify a series of neutral THIQ analogs that bind to KEAP1 in the low micromolar range. These analogs establish new H-bond interactions at the P3 and P2 pockets allowing the replacement of the carboxylic acid functionality by a neutral primary carboxamide. X-ray crystallog. studies reveal the novel binding mode of these mols. to KEAP1.
ACS Medicinal Chemistry Letters published new progress about 27943-46-0. 27943-46-0 belongs to tetrahydropyran, auxiliary class Tetrahydropyran,Alkynyl,Ether, name is 2-((2-Methylbut-3-yn-2-yl)oxy)tetrahydro-2H-pyran, and the molecular formula is C10H16O2, Product Details of C10H16O2.
Referemce:
https://en.wikipedia.org/wiki/Tetrahydropyran,
Tetrahydropyran – an overview | ScienceDirect Topics