RT Journal Article T1 11PS04 is a new chemical entity identified by microRNA-based biosensing with promising therapeutic potential against cancer stem cells A1 Aguado Sánchez, Tania A1 Romero-Revilla, José A1 Granados, Rosario A1 Campuzano Ruiz, Susana A1 Torrente Rodríguez, Rebeca Magnolia A1 Cuesta Martínez, Ángel A1 Albiñana, Virginia A1 Botella, Luisa María A1 Santamaría, Silvia A1 Garcia-Sanz, Jose A1 Pingarrón Carrazón, José Manuel A1 Sánchez-Sancho, Francisco A1 Sánchez-Puelles, José-María AB Phenotypic drug discovery must take advantage of the large amount of clinical data currently available. In this sense, the impact of microRNAs (miRs) on human disease and clinical therapeutic responses is becoming increasingly well documented. Accordingly, it might be possible to use miR-based signatures as phenotypic read-outs of pathological status, for example in cancer. Here, we propose to use the information accumulating regarding the biology of miRs from clinical research in the preclinical arena, adapting it to the use of miR biosensors in the earliest steps of drug screening. Thus, we have used an amperometric dual magnetosensor capable of monitoring a miR-21/miR-205 signature to screen for new drugs that restore these miRs to non-tumorigenic levels in cell models of breast cancer and glioblastoma. In this way we have been able to identify a new chemical entity, 11PS04 ((3aR,7aS)-2-(3-propoxyphenyl)-7,7a-dihydro-3aH-pyrano[3,4-d]oxazol-6(4H)-one), the therapeutic potential of which was suggested in mechanistic assays of disease models, including 3D cell culture (oncospheres) and xenografts. These assays highlighted the potential of this compound to attack cancer stem cells, reducing the growth of breast and glioblastoma tumors in vivo. These data demonstrate the enhanced chain of translatability of this strategy, opening up new perspectives for drug-discovery pipelines and highlighting the potential of miR-based electro-analytical sensors as efficient tools in modern drug discovery. PB Nature Research YR 2019 FD 2019 LK https://hdl.handle.net/20.500.14352/91612 UL https://hdl.handle.net/20.500.14352/91612 LA eng NO Aguado, T., Romero-Revilla, J.A., Granados, R. et al. 11PS04 is a new chemical entity identified by microRNA-based biosensing with promising therapeutic potential against cancer stem cells. Sci Rep 9, 11916 (2019). https://doi.org/10.1038/s41598-019-48359-y NO Ministerio de Economía, Industria y Competitividad (España) NO Comunidad de Madrid NO Instituto de Salud Carlos III NO Centro de Investigación Biomédica en Red de Enfermedades Respiratorias NO European Commission DS Docta Complutense RD 13 abr 2025