- Ana B. García
- Cristina Ana Gómez
- Esther González
- Sonsoles Rodríguez
- Carmen Varela
- Javier Sánchez
The Medicinal Chemistry Section is part of the multidisciplinary Experimental Therapeutics Programme (ETP) that is focused on early drug discovery activities. Our aim is to generate advanced chemical compounds that could be further developed into drugs to treat cancer. The Section deals with the design, synthesis, and optimisation of compounds that are characterised in the Biology Section of ETP to evaluate their potency in biological targets, in vitro and in vivo drug-like properties and, finally, to demonstrate their efficacy and mechanism of action in animal models (in vivo proof-of-concept). As a complementary strategy to the classic inhibitors, we also contemplate the degradation of particular targets using different chemical approaches such as the use of proteolysis targeting chimeras (PROTACs). Additionally, we have entered the chemical biology field in order to discover and identify novel drugs and targets from phenotypic screenings. In this regard, we contribute by synthesising high quality chemical tools needed for interrogating the observed phenotype.
- (2021). Omipalisib inspired macrocycles as dual PI3K/mTOR inhibitors.. Eur J Med Chem 211, 113109. CNIO Publication.
- (2021). Macrocyclization as a source of desired polypharmacology. Discovery of triple PI3K/mTOR/PIM inhibitors.. ACS Med Chem Lett 12, 1794-1801. CNIO Publication.
- (2020). Global hyperactivation of enhancers stabilizes human and mouse naive pluripotency through inhibition of CDK8/19 Mediator kinases. Nat Cell Biol 22, 1223-1238. CNIO Publication.
- (2020). Anti?tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL?302 in neuroblastoma. EMBO Mol Med 12, e11749. CNIO Publication.
- (2020). Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer.. Oncogene 39, 3028-3040. CNIO Publication.
- (2020). Induction of Lysosome Membrane Permeabilization as a Therapeutic Strategy to Target Pancreatic Cancer Stem Cells. Cancers 12, 1790. CNIO Publication. Open Access
- (2020). Screening protocol for the identification of modulators by immunofluorescent cell-based assay. Chem Biol Drug Des 95, 66-78. CNIO Publication.
- (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
- (2019). Multiple cancer pathways regulate telomere protection.. EMBO Mol Med 11, e10292. CNIO Publication. Open Access
- (2019). Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma.. EMBO Mol Med 11, e10058. CNIO Publication. Open Access
- (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.