Sonia Martínez Head of Section
T +34 (+34) 917 328 000 (Ext 3739)
smartinezg@cnio.es

The Medicinal Chemistry Section is part of the interdisciplinary Experimental Therapeutics Programme that is dedicated to early Drug Discovery in the oncology field. Our aim is to discover new anticancer agents based on the hypotheses and targets generated by CNIO’s Basic Research Groups; this is done in close collaboration with these Groups. Medicinal Chemistry activities start with the identification of hits through High Throughput Screening (HTS) campaigns from targeted or phenotypic assay or hits generated in our Section by applying Rational Drug Design Strategies; these are then optimised to obtain novel lead compounds with in vivo activity in different animal models. For hits obtained from phenotypic screenings, we help to decipher the mechanism of action responsible for the observed phenotype, synthesising affinity probes that will be used for cellular localisation (imaging techniques) and extracting the target/s (pull down experiments). We are also developing PROTACs (proteolysis targeting chimeras) as promoters of cell protein degradation to establish their applicability across diverse drug discovery projects.

Publications

• 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.
• 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.
• López-Guadamillas E, Muñoz-Martin M, Martinez S, Pastor J, Fernandez-Marcos PJ, Serrano M (2016). PI3K inhibition reduces obesity in mice.. Aging (Albany NY) 8, 2747-2753. 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.
• Ortega-Molina A, Lopez-Guadamillas E, Mattison JA, Mitchell SJ, Muñoz-Martin M, Iglesias G, Gutierrez VM, Vaughan KL, Szarowicz MD, González-García I, López M, Cebrián D, Martinez S, Pastor J, de Cabo R, Serrano M (2015). Pharmacological inhibition of PI3K reduces adiposity and metabolic syndrome in obese mice and rhesus monkeys.. Cell Metab 21, 558-570. CNIO Publication.
• García-Beccaria M, Martínez P, Méndez-Pertuz M, Martínez S, Blanco-Aparicio C, Cañamero M, Mulero F, Ambrogio C, Flores JM, Megias D, Barbacid M, Pastor J, Blasco MA (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.
• Alonso-Curbelo D, Osterloh L, Cañón E, Calvo TG, Martínez-Herranz R, Karras P, Martínez S, Riveiro-Falkenbach E, Romero PO, Rodríguez-Peralto JL, Pastor J, Soengas MS (2015). RAB7 counteracts PI3K-driven macropinocytosis activated at early stages of melanoma development.. Oncotarget 6, 11848-11862. CNIO Publication.