Biology Section

Carmen Blanco Head of Section
T +34 917328000 (Ext 3780)
cblanco@cnio.es

Post-Doctoral Fellows

María Elena Hernández

Technicians

Mª Isabel Albarrán
Antonio Cebriá
Elena Gómez-Casero
Javier Klett
Mª del Carmen Rodríguez de Miguel

In the Experimental Therapeutics Programme, we perform both phenotypic and targeted-based drug discovery. The Biology Section is devoted to the biochemical, cellular, and in vitro/in vivo pharmacological characterisation of the compounds synthesised within the Programme.

At the biochemical assay level, we have developed a panel of different biochemical assays and optimised them for the targets used in our screening campaigns. We have currently established more than 30 different types of biochemical assays, mainly focused on kinase activities and covering a broad range of sensitivities and technologies (FI, FP, FRET, TR-FRET, chemiluminiscence, coupled enzymatic reactions, binding assays, etc.) adapted to the targets that we have been working on.

Recently, in order to identify inhibitors of relevant cancer targets with no enzymatic activity, we have started to develop biochemical assays to measure protein/protein interaction and protein/DNA interactions. These assays are based on AlphaScreen and AlphaLISA technology.

Publications

Martínez-González S, García AB, Albarrán MI, Cebriá A, Amezquita-Alves A, García-Campos FJ, Martínez-Gago J, Martínez-Torrecuadrada J, Muñoz I, 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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication. 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. CNIO Publication.
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. CNIO Publication. 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. CNIO Publication. 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. CNIO Publication.
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. CNIO Publication. 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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication. Open Access
Jiménez-García MP, Lucena-Cacace A, Robles-Frías MJ, Narlik-Grassow M, Blanco-Aparicio C, Carnero A (2016). The role of PIM1/PIM2 kinases in tumors of the male reproductive system.. Sci Rep 6, 38079. CNIO Publication.
Aragoneses-Fenoll L, Montes-Casado M, Ojeda G, Acosta YY, Herranz J, Martínez S, Blanco-Aparicio C, Criado G, Pastor J, Dianzani U, Portolés P, Rojo JM (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.
Mosteiro LL, Pantoja C, Alcazar N, Marión RM, Chondronasiou D, Rovira M, Fernandez-Marcos PJ, Muñoz-Martin M, Blanco-Aparicio C, Pastor J, Gómez-López G, de Martino A, Blasco MA, Abad M, Serrano M (2016). Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.. Science 354, pii: aaf4445.. CNIO Publication.