Identification of a Sonically Activated Degrader of Methionine Adenosyltransferase 2A by an Approach Assisted with the Hole-Electron Analysis.

Small molecules capable of modulating methionine adenosyltransferase 2A (MAT2A) are of significant interest in precise cancer therapeutics. Herein, we raised the hole-electron Coulombic attraction as a reliable molecular descriptor for predicting the reactive oxygen generation capacity of MAT2A inhibitors, based on which we discovered compound as a sonically activated degrader of MAT2A. Upon sonication, can generate reactive oxygen species to specifically degrade cellular MAT2A via rapid oxidative reactions.

Construction of benzofuranone library via a metal-free, one-pot intermolecular condensation, and their application as efficient estrogen receptor β modulators.

Facile synthesis of benzofuranone was achieved through a metal-free, one-pot intermolecular condensation between α-hydroxy aryl ketones and resorcinol derivatives. A library of 20 compounds with moderate to good overall yields was prepared. These compounds showed strong binding toward estrogen receptors along with good selectivity for ERβ (>190-fold over ERα).