Becarios Post-doctorales
- María Elena Hernández
Técnicos de Laboratorio
- Mª Isabel Albarrán
- Antonio Cebriá
- Elena Gómez-Casero
- Javier Klett
- María Martín
- Mª del Carmen Rodríguez de Miguel
The early Drug Discovery (eDD) process encompasses screening campaigns for hit identification, hit generation and hit lo lead and lead optimisation phases, in order to end up with a lead compound able to demonstrate in vivo proof-of-concept. ADME, an acronym for absorption, distribution, metabolism and excretion, describes the disposition of a pharmaceutical compound within an organism. ADME properties influence the drug levels and the kinetics of drug exposure to the tissues, and hence influence the performance and pharmacological activity of the compound as a drug. It is fundamental to assess the parameters for ADME properties early on during the discovery stage, since they provide critical information that can help to better interpret the screening results and to design new molecules. Drug-like properties should be optimised in parallel to pharmacological activity against the target. For that reason, we perform ADME characterisation of the compounds during the initial steps of eDD projects and we carry out PK, PK/PD and distribution studies to validate the drug properties of our advanced molecules.
Publicaciones
- (2019). Screening protocol for the identification of modulators by immunofluorescent cell-based assay. Chem Biol Drug Des (in press). Publicación CNIO.
- (2019). Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma.. EMBO Mol Med 11, e10058. Publicación CNIO.
Open Access - (2019). Discovery of novel triazolo[4,3-b]pyridazin-3-yl-quinoline derivatives as PIM inhibitors. Eur J Med Chem 168, 87-109. Publicación CNIO.
- (2018). Exome Sequencing of Plasma DNA Portrays the Mutation Landscape of Colorectal Cancer and Discovers Mutated VEGFR2 Receptors as Modulators of Antiangiogenic Therapies. Clin Cancer Res 24, 3550-3559. Publicación CNIO.
- (2018). STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nat Med 24, 1024-1035. Publicación CNIO.
- (2017). Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus. Oncotarget 8, 58872-58886. Publicación CNIO.
- (2017). Identification of novel PI3K inhibitors through a scaffold hopping strategy.. Bioorg Med Chem Lett 27, 4794-4799. Publicación CNIO.
- (2017). Generation of tricyclic imidazo[1,2-a]pyrazines as novel PI3K inhibitors by application of a conformational restriction strategy.. Bioorg Med Chem Lett 27, 2536-2543. Publicación CNIO.
- (2017). Inhibition of Trf1 telomere protein impairs tumor initiation and progression in glioblastoma multiform mouse models and patient-derived xenografts.. Cancer Cell 32, 590-607. Publicación CNIO.
- (2017). Modulation of telomere protection by the PI3K/AKT pathway. Nat Commun 8, 1278. Publicación CNIO. Open Access
- (2016). The role of PIM1/PIM2 kinases in tumors of the male reproductive system.. Sci Rep 6, 38079. Publicación CNIO.
- (2016). ETP-46321, a dual p110a/d class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis. Biochem Pharmacol 106, 56-59. Publicación CNIO.
- (2016). Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.. Science 354, pii: aaf4445.. Publicación CNIO.
- (2015). Therapeutic inhibition of TRF1 impairs the growth of p53-deficient K-RasG12V-induced lung cancer by induction of telomeric DNA damage.. EMBO Mol Med 7, 930-949. Publicación CNIO.
- (2014). Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis.. Bmc Cancer 14, 281. Publicación CNIO.
- (2014). Genetic Modeling of PIM Proteins in Cancer: Proviral Tagging and Cooperation with Oncogenes, Tumor Suppressor Genes, and Carcinogens.. Front Oncol 4, 109. Publicación CNIO.
- (2014). Non-genotoxic activation of p53 through the RPL11-dependent ribosomal stress pathway.. Carcinogenesis 35, 2822-2830. Publicación CNIO.