“Este contenido se encuentra unicamente en inglés”
- Ana B. García
- Cristina Ana Gómez
- Esther González
- Ana I. Hernández
- Sonsoles Rodríguez
- Carmen Varela
- Francisco Javier García
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.
- PI3K inhibition reduces obesity in mice.(2016)
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)
Biochem Pharmacol 106, 56-59.
- Pharmacological inhibition of PI3K reduces adiposity and metabolic syndrome in obese mice and rhesus monkeys.(2015)
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)
EMBO Mol Med 7, 930-949.
- RAB7 counteracts PI3K-driven macropinocytosis activated at early stages of melanoma development.(2015)
Oncotarget 6, 11848-11862.
- Non-genotoxic activation of p53 through the RPL11-dependent ribosomal stress pathway.(2014)
Carcinogenesis 35, 2822-2830.
- Biological characterization of ETP-46321 a selective and efficacious inhibitor of phosphoinositide-3-kinases.(2013)
Invest New Drug 31, 66-76.