- María Elena Hernández
Técnicos de Laboratorio
- Mª Isabel Albarrán
- Antonio Cebriá
- Elena Gómez-Casero
- Javier Klett
- 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.
- (2019). Discovery of novel triazolo[4,3-b]pyridazin-3-yl-quinoline derivatives as PIM inhibitors. Eur J Med Chem 168, 87-109.
- (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.
- (2018). STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nat Med 24, 1024-1035.
- (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.
- (2017). Modulation of telomere protection by the PI3K/AKT pathway.. Nat Commun 8, 1278.
- (2017). Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus. Oncotarget 8, 58872-58886.
- (2017). Identification of novel PI3K inhibitors through a scaffold hopping strategy.. Bioorg Med Chem Lett 27, 4794-4799.
- (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.
- (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.
- (2016). Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.. Science 354, pii: aaf4445..
- (2016). The role of PIM1/PIM2 kinases in tumors of the male reproductive system.. Sci Rep 6, 38079.
- (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.
- (2014). Non-genotoxic activation of p53 through the RPL11-dependent ribosomal stress pathway.. Carcinogenesis 35, 2822-2830.
- (2014). Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis.. Bmc Cancer 14, 281.
- (2014). Genetic Modeling of PIM Proteins in Cancer: Proviral Tagging and Cooperation with Oncogenes, Tumor Suppressor Genes, and Carcinogens.. Front Oncol 4, 109.
- (2013). Biological characterization of ETP-46321 a selective and efficacious inhibitor of phosphoinositide-3-kinases.. Invest New Drug 31, 66-76.
- (2013). The PIM Family of Serine/Threonine Kinases in Cancer.. Med Res Rev 34, 136-159.
- (2013). Simultaneous inhibition of pan-phosphatidylinositol-3-kinases and MEK as a potential therapeutic strategy in peripheral T-cell lymphomas.. Haematologica 98, 57-64.
- (2013). Pim kinases in cancer: diagnostic, prognostic and treatment opportunities.. Biochem Pharmacol 85, 623-643.
- (2013). Conditional transgenic expression of PIM1 kinase in prostate induces inflammation-dependent neoplasia.. PLoS ONE 8, e60277.