- María Elena Hernández
- Mª Isabel Albarrán
- Antonio Cebriá
- Elena Gómez-Casero
- Javier Klett
Target Engagement assays measure compound binding to a selected target protein inside living cells and enable making correlations with biochemical activity. BRET or bioluminescence resonance energy transfer can be used to study cellular target engagement. NanoBRET assays are based on the fact that NanoLuc luciferase fusion proteins expressed in cells can transfer energy to a proximal fluorophore called tracer. Compound affinity to a given protein can be measured by competitive displacement of the tracer reversibly bound to the corresponding NanoLuc luciferase fusion protein in cells. In the case of PROTACs (Proteolysis Targeting Chimeras), target engagement assays are essential to evaluate the affinity of PROTACs to both the target protein and the E3 ligase, as binding to both is required for the formation of the ternary complex, which triggers the degradation of the target protein. We apply BRET assays routinely in our projects to help in the optimisation of our molecules.
- (2021). Screening health-promoting compounds for their capacity to induce the activity of FOXO3. J Gerontol A-Biol (in press). CNIO Publication.
- (2021). Co-Targeting PIM Kinase and PI3K/mTOR in NSCLC.. Cancers 13, 2139. CNIO Publication.
- (2020). Pyrido[2,3-b][1,5]benzoxazepin-5(6H)-one derivatives as CDK8 inhibitors.. Eur J Med Chem 201, 112443. CNIO Publication.
- (2020). Tumor regression and resistance mechanisms upon CDK4 and RAF1 inactivation in KRAS/P53 mutant lung adenocarcinomas. Proc Natl Acad Sci USA 117, 24415-24426. CNIO Publication.
- (2020). Screening protocol for the identification of modulators by immunofluorescent cell-based assay. Chem Biol Drug Des 95, 66-78. CNIO Publication.
- (2020). Anti?tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL?302 in neuroblastoma. EMBO Mol Med 12, e11749. CNIO Publication.
- (2020). Induction of Lysosome Membrane Permeabilization as a Therapeutic Strategy to Target Pancreatic Cancer Stem Cells. Cancers 12, 1790. CNIO Publication. Open Access
- (2020). Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer.. Oncogene 39, 3028-3040. CNIO Publication.
- (2019). Disulfide Engineered Lipase to Enhance the Catalytic Activity: A Structure-Based Approach on BTL2.. Int J Mol Sci 20, E5245. CNIO Publication. Open Access
- (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. Open Access
- (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