Identification of small compounds regulating the secretion of extracellular vesicles via a TIM4-affinity ELISA

Abstract Extracellular vesicles (EVs) are secreted from most cells and play important roles in cell–cell communication by transporting proteins, lipids, nucleic acids. As the involvement of EVs diseases has become apparent, druggable regulators EV secretion required. However, lack a highly sensitive detection system made development difficult. We developed an ELISA using high-affinity phosphatidylserine-binder TIM4 to capture screened 1567-compound library. Consequently, we identified one inhibitor three activators variety cells. The inhibitor, apoptosis activator 2, suppressed via different mechanism had broader cellular specificity than GW4869. Moreover, activators, namely cucurbitacin B, gossypol, obatoclax, broad specificity, including HEK293T human mesenchymal stem (hMSCs). In vitro bioactivity assays revealed that some control glioblastoma hMSCs, which induces angiogenesis protects cardiomyocytes against apoptosis, respectively. conclusion, high-throughput method detect with high sensitivity versatility, four compounds can regulate EVs.