Sección de Biología

Inicio | Investigación e innovación | Programas Científicos | Programa de Terapias Experimentales | Sección de Biología

Investigadores Científicos

  • Pablo Aparicio
  • Marta San Martín

Becarios Post-doctorales

  • María Elena Hernández

Becarios Pre-Doctorales

  • Lucía Cañizares

Técnicos de Laboratorio

  • Mª Isabel Albarrán
  • Antonio Cebriá
  • Claudia Díaz
  • Elena Gómez-Casero

A high-quality small-molecule probe for target validation has to be cell permeable and demonstrate target engagement and selectivity, as well as pharmacological and phenotypic response. PROTACs (PROteolysis TArgeting Chimeras) have emerged as new promising pharmacological modalities. Moreover, PROTACs represent the chemical equivalent of small interfering RNA (siRNA), albeit allowing removal of a protein at a post-translational level. Parameters such as the maximum level of target degradation (Dmax), confirmation of a proteasome dependent degradation mechanism, and kinetic parameters of POI degradation and selective degradation have to be taken into account to use PROTACs for target validation. In collaboration with Marcos Malumbres, we started an early drug discovery project to develop MASTL inhibitors and PROTACs, as non-advanced inhibitors have already been described. We have been able to develop both types of molecules, generating a set of PROTACS that meet the requirements to be used as chemical tools for target validation and to define their clinical niche.