Piezo1 is a member of the mechanosensitive piezo ion channel family, which transduces various mechanical stimulations into electrochemical signals. Piezo1 is closely implicated in different physiological processes ranging from erythrocyte volume homeostasis to lymphatic vessel formation and bone homeostasis. Aberrant Piezo1 functions caused by gain-of-function or loss-of-function mutations are associated with various pathological conditions. Due to the significant contribution on the recognition of Piezo ion channels for sensing mechanical stress, Ardem Patapoutian received the 2021 Nobel Prize in Physiology or Medicine (jointly). Strategies of targeting and modulating Piezo1 have shown potential to produce significant therapeutic effects, thus validating Piezo1 as a promising drug target for diseases. In this Perspective, we review the cryo-EM structure, mechanogating mechanism, and physiological profiles of Piezo1, together with the latest advances in the development of its modulators. Limitations and challenges as well as future development of Piezo1 modulators are discussed as well.

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A robust Stille gem-difluoroallylation of arylstannanes with 3-bromo-3,3-difluoropropenes has been established. The catalyst was found to exert critical effect on the reaction chemoselectivity. By using Pd­(OH)2/C as the catalyst, a series of 3-(hetero)­aryl/vinyl-3,3-difluoropropenes were obtained in high efficiency with α-substitution regioselectivity. The reaction has a broad substrate scope, and various substitution patterns were well tolerated in both substrates. Notably, the reaction can be easily extended to late-stage gem-difluoroallylation of many bioactive molecules with good chemoselectivity.

The gem-difluoroallyl group is a sought-after structural motif commonly found in pharmaceutical compounds. Despite its appeal, achieving a controlled synthesis of both α,αand γ,γ-difluoroallylated compounds has proven to be a challenging task. This study presents a new approach to difluoroallylation, which utilizes a regiodivergent C−H bond reaction catalyzed by ruthenium catalysis. This method enables the meta and ortho C−H α,αand ortho C−H γ,γ-difluoroallylation of arenes using 3-bromo-3,3difluoropropenes.