- María Elena Hernández
- 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.
- (2019). Disulfide Engineered Lipase to Enhance the Catalytic Activity: A Structure-Based Approach on BTL2.. Int J Mol Sci 20, E5245. CNIO Publication.
- (2019). Screening protocol for the identification of modulators by immunofluorescent cell-based assay. Chem Biol Drug Des (in press). CNIO Publication.
- (2019). Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma.. EMBO Mol Med 11, e10058. CNIO Publication. 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. CNIO Publication.
- (2019). The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status.. Nat Commun 10, 5428. CNIO Publication.
- (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. CNIO Publication.
- (2018). STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nat Med 24, 1024-1035. CNIO Publication.
- (2017). Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus. Oncotarget 8, 58872-58886. CNIO Publication.
- (2017). Identification of novel PI3K inhibitors through a scaffold hopping strategy.. Bioorg Med Chem Lett 27, 4794-4799. CNIO Publication.
- (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. CNIO Publication.
- (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. CNIO Publication.
- (2017). Modulation of telomere protection by the PI3K/AKT pathway. Nat Commun 8, 1278. CNIO Publication. Open Access
- (2016). The role of PIM1/PIM2 kinases in tumors of the male reproductive system.. Sci Rep 6, 38079. CNIO Publication.
- (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. CNIO Publication.
- (2016). Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.. Science 354, pii: aaf4445.. CNIO Publication.
- (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. CNIO Publication.
- (2015). Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogenesis 36, S254-S296. CNIO Publication.
- (2014). Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis.. Bmc Cancer 14, 281. CNIO Publication.
- (2014). Genetic Modeling of PIM Proteins in Cancer: Proviral Tagging and Cooperation with Oncogenes, Tumor Suppressor Genes, and Carcinogens.. Front Oncol 4, 109. CNIO Publication.
- (2014). Non-genotoxic activation of p53 through the RPL11-dependent ribosomal stress pathway.. Carcinogenesis 35, 2822-2830. CNIO Publication.