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Internalization and intracellular trafficking of hormone receptors, like receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs), play pivotal roles in cell responsiveness homeostasis. Dysregulation in receptor trafficking can lead to aberrant signaling and cell behavior, prevalent in cancer. Here, using an endosomal BRET-based assay in a high-throughput screen with the prototypical GPCR angiotensin II type 1 receptor (AT1R), we sought to identify inhibitors of receptor trafficking from a library of ~115,000 small molecules. We identified a novel dual Ras and ARF6 inhibitor that blocks agonist-mediated internalization of AT1R and other GPCRs, which we named Rasarfin. Rasarfin also potently inhibited agonist-induced ERK1/2 signaling by GPCRs, and MAPK and Akt signaling by EGFR, as well as prevented cancer cell proliferation. In silico modeling and in vitro studies revealed a unique binding modality of Rasarfin within the SOS-binding domain of Ras. Our findings unveil a new class of dual small G protein inhibitors for receptor trafficking and signaling, useful for the inhibition of oncogenic cellular responses.

In a context of growing electrification of road transport, Wireless Power Transfer (WPT) appears as an appealing alternative technology as it enables Electric Vehicles (EVs) to charge while driving and without any mechanical contact (with overhead cables or rails in the ground). Although the WPT technology background dates from the end of 20th century, recent advances in semiconductor technologies have enabled the first real demonstrations. Within the FABRIC European project, the French research Institute VEDECOM and its partners implemented a whole prototype wireless power transfer charging infrastructure. The first demonstrations of Inductive WPT in different real driving conditions (up to 20 kW, from 0 to 100 km/h, with one or two serial vehicles) were provided. This paper describes the prototype equipment and its instrumentation and provides the system characterization results. The future of the Inductive WPT technology is further discussed considering its different technical and economic challenges. In parallel, how this technology could be part of future generation road infrastructures is discussed. Future research and demonstration steps are presented in the conclusion.