“Este contenido se encuentra unicamente en inglés”

Sonia Martínez Jefe de Sección
T +34 (+34) 917 328 000 (Ext 3739)
smartinezg@cnio.es

The Medicinal Chemistry Section is part of the Experimental Therapeutics Interdisciplinary Programme that is dedicated to early Drug Discovery activities in the oncology field. Medicinal Chemistry activities start with the identification of hits through high throughput screening campaigns from targeted or phenotypic assays, and lead on to further activities related to the design, synthesis and optimisation of the compounds in order to obtain novel lead compounds with in vivo activity in appropriate animal models. For hits obtained from phenotypic screenings we introduce an additional target identification step in order to decipher the mechanism of action responsible for the observed phenotype. Our Group has experience in the design and synthesis of affinity probes for target deconvolution studies. These molecules enable the detection of the cellular localisation of the target of interest through imaging techniques and enable its isolation through pull-down experiments. Additionally, as a complementary alternative, we are developing proteolysis targeting chimeras (PROTACs) as promoters of cellular protein degradation in order to establish their applicability across diverse drug discovery projects.

Publicaciones

• PI3K inhibition reduces obesity in mice.(2016)
  López-Guadamillas E, Muñoz-Martin M, Martinez S, Pastor J, Fernandez-Marcos PJ, Serrano M
  Aging (Albany NY) 8, 2747-2753.
• ETP-46321, a dual p110a/d class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis(2016)
  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
  Biochem Pharmacol 106, 56-59.
• Pharmacological inhibition of PI3K reduces adiposity and metabolic syndrome in obese mice and rhesus monkeys.(2015)
  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
  Cell Metab 21, 558-570.
• Therapeutic inhibition of TRF1 impairs the growth of p53-deficient K-RasG12V-induced lung cancer by induction of telomeric DNA damage.(2015)
  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
  EMBO Mol Med 7, 930-949.
• RAB7 counteracts PI3K-driven macropinocytosis activated at early stages of melanoma development.(2015)
  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
  Oncotarget 6, 11848-11862.
• Non-genotoxic activation of p53 through the RPL11-dependent ribosomal stress pathway.(2014)
  Morgado-Palacin L, Llanos S, Urbano M, Blanco-Aparicio C, Megias D, Pastor J, Serrano M
  Carcinogenesis 35, 2822-2830.
• Biological characterization of ETP-46321 a selective and efficacious inhibitor of phosphoinositide-3-kinases.(2013)
  Granda TG, Cebrián D, Martínez S, Anguita PV, López EC, Link W, Merino T, Pastor J, Serelde BG, Peregrina S, Palacios I, Albarran MI, Cebriá A, Lorenzo M, Alonso P, Fominaya J, López AR, Bischoff JR
  Invest New Drug 31, 66-76.