Sección de Biología

Carmen Blanco Jefe de Sección
T +34 917328000 (Ext 3780)
cblanco@cnio.es

Becarios Post-doctorales

María Elena Hernández

Técnicos de Laboratorio

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.

Publicaciones

Jimenez L, Silva A, Calissi G, Grenho I, Monteiro R, Mayoral-Varo V, Blanco-Aparicio C, Pastor J, Bustos V, Bracher F, Megías D, Ferreira BI, Link W (2021). Screening health-promoting compounds for their capacity to induce the activity of FOXO3. J Gerontol A-Biol (in press). Publicación CNIO.
Moore G, Lightner C, Elbai S, Brady L, Nicholson S, Ryan R, O'Sullivan KE, O'Byrne KJ, Blanco-Aparicio C, Cuffe S, O'Neill M, Heavey S, Finn SP, Gately K (2021). Co-Targeting PIM Kinase and PI3K/mTOR in NSCLC.. Cancers 13, 2139. Publicación CNIO.
Martínez-González S, García AB, Albarrán MI, Cebriá A, Amezquita-Alves A, García-Campos FJ, Martínez-Gago J, Martínez-Torrecuadrada J, Muñoz IG, Blanco-Aparicio C, Pastor J (2020). Pyrido[2,3-b][1,5]benzoxazepin-5(6H)-one derivatives as CDK8 inhibitors.. Eur J Med Chem 201, 112443. Publicación CNIO.
Esteban-Burgos L, Wang H, Nieto P, Zheng J, Blanco-Aparicio C, Varela C, Gómez-López G, Fernández-García F, Sanclemente M, Guerra C, Drosten M, Galán J, Caleiras E, Martínez-Torrecuadrada J, Fajas L, Peng SB, Santamaría D, Musteanu M, Barbacid M (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. Publicación CNIO.
Klett J, Gómez-Casero E, Méndez-Pertuz M, Urbano-Cuadrado M, Megias D, Blasco MA, Martínez S, Pastor J, Blanco-Aparicio C (2020). Screening protocol for the identification of modulators by immunofluorescent cell-based assay. Chem Biol Drug Des 95, 66-78. Publicación CNIO.
Mohlin S, Hansson K, Radke K, Martinez S, Blanco-Apiricio C, Garcia-Ruiz C, Welinder C, Esfandyari J, O'Neill M, Pastor J, von Stedingk K, Bexell D (2020). Anti?tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL?302 in neuroblastoma. EMBO Mol Med 12, e11749. Publicación CNIO.
Cash TP, Alcalá S, Rico-Ferreira MDR, Hernández-Encinas E, García J, Albarrán MI, Valle S, Muñoz J, Martínez-González S, Blanco-Aparicio C, Pastor J, Serrano M, Sainz B Jr (2020). Induction of Lysosome Membrane Permeabilization as a Therapeutic Strategy to Target Pancreatic Cancer Stem Cells. Cancers 12, 1790. Publicación CNIO. Open Access
Kennedy SP, O'Neill M, Cunningham D, Morris PG, Toomey S, Blanco-Aparicio C, Martinez S, Pastor J, Eustace AJ, Hennessy BT (2020). Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer.. Oncogene 39, 3028-3040. Publicación CNIO.
Godoy CA, Klett J, Di Geronimo B, Hermoso JA, Guisán JM, Carrasco-López C (2019). Disulfide Engineered Lipase to Enhance the Catalytic Activity: A Structure-Based Approach on BTL2.. Int J Mol Sci 20, E5245. Publicación CNIO. Open Access
Mohlin S, Hansson K, Radke K, Martinez S, Blanco-Aparicio C, Garcia-Ruiz C, Welinder C, Esfandyari J, O'Neill M, Pastor J, von Stedingk K, Bexell D (2019). Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma.. EMBO Mol Med 11, e10058. Publicación CNIO. Open Access
Martínez-González S, Rodríguez-Arístegui S, Gómez de la Oliva CA, Hernández AI, González Cantalapiedra E, Varela C, García AB, Rabal O, Oyarzabal J, Bischoff JR, Klett J, Albarrán MI, Cebriá A, Ajenjo N, García-Serelde B, Gómez-Casero E, Cuadrado-Urbano M, Cebrián D, Blanco-Aparicio C, Pastor J (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.
Trigg RM, Lee LC, Prokoph N, Jahangiri L, Reynolds CP, Amos Burke GA, Probst NA, Han M, Matthews JD, Kai Lim H, Manners E, Martinez S, Pastor J, Blanco-Aparicio C, Merkel O, de Los Fayos Alonso IG, Kodajova P, Tangermann S, Högler S, Luo J, Kenner L, Turner SD. (2019). The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status.. Nat Commun 10, 5428. Publicación CNIO. Open Access
Toledo RA, Garralda E, Mitsi M, Pons T, Monsech J, Vega E, Otero Á, Albarran MI, Baños N, Durán Y, Bonilla V, Sarno F, Camacho-Artacho M, Sanchez-Perez T, Perea S, Álvarez R, De Martino A, Lietha D, Blanco-Aparicio C, Cubillo A, Domínguez O, Martínez-Torrecuadrada JL, Hidalgo M (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.
Priego N, Zhu L, Monteiro C, Mulders M, Wasilewski D, Bindeman W, Doglio L, Martínez L, Martínez-Saez E, Cajal SRY, Megías D, Hernández-Encinas E, Blanco-Aparicio C, Martínez L, Zarzuela E, Muñoz J, Fustero-Torres C, Pineiro E, Hernández-Laín A, Bertero L, Poli V, Sánchez-Martínez M, Menendez JA, Soffietti R, Bosch-Barrera J, Valiente M (2018). STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nat Med 24, 1024-1035. Publicación CNIO.
Jiménez-García MP, Lucena-Cacace A, Robles-Frías MJ, Ferrer I, Narlik-Grassow M, Blanco-Aparicio C, Carnero A (2017). Inflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uterus. Oncotarget 8, 58872-58886. Publicación CNIO.
Martínez González S, Hernández AI, Álvarez RM, Rodríguez A, Ramos-Lima F, Bischoff JR, Albarrán MI, Cebriá A, Hernández-Encinas E, García-Arocha J, Cebrián D, Blanco-Aparicio C, Pastor J. (2017). Identification of novel PI3K inhibitors through a scaffold hopping strategy.. Bioorg Med Chem Lett 27, 4794-4799. Publicación CNIO.
Martínez González S, Rodríguez-Arístegui S, Hernández AI, Varela C, González Cantalapiedra E, Álvarez RM, Rodríguez Hergueta A, Bischoff JR, Albarrán MI, Cebriá A, Cendón E, Cebrián D, Alfonso P, Pastor J. (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.
Bejarano L, Schuhmacher AJ, Méndez-Pertuz M, Megías M, Blanco-Aparicio C, Martínez S, Pastor J, Squatrito M, Blasco MA (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.
Méndez-Pertuz M, Martínez P, Blanco-Aparicio C, Gómez-Casero E, García AB, Martínez -Torrecuadrada J, Palafox M, Cortés J, Serra V, Pastor J, Blasco MA (2017). Modulation of telomere protection by the PI3K/AKT pathway. Nat Commun 8, 1278. Publicación CNIO. Open Access