Research team
Characterization and validation of novel autophagy inducers identified via high-throughput screening: a therapeutic option for the treatment of advanced atherosclerosis.
Abstract
Autophagy is a highly conserved intracellular recycling process that removes unnecessary or dysfunctional cellular components from the cytoplasm. Defective autophagy is a main feature of several human pathologies such as neurodegeneration, cancer and cardiovascular disease. Accordingly, there is strong interest in pharmacological agents that stimulate autophagy. Yet, the unequivocal validation of autophagy induction as a therapeutic strategy is currently lacking. Many obstacles remain, including the absence of potent, selective, and druglike autophagy inducers and easily transmissible preclinical results obtained with such compounds. This project aims to address the existing limitations in the field. We recently performed a phenotypic high-throughput screen on a library of diverse lead-like molecules and several novel autophagy-inducing molecules were identified. Moreover, derivatives of the initial hits were synthesized in order to obtain drug-like compounds with a more favorable biopharmaceutical profile. In this proposal, the autophagy-inducing potency and pharmacokinetic profile of the identified hits and derivatives will be thoroughly characterized both in vitro and in vivo. Moreover, the most promising autophagy inducer will be tested in a mouse model of advanced atherosclerosis. We expect that the knowledge and molecular tools generated by this project will have a major impact on (pre)clinical drug research and may improve human health through autophagy induction.Researcher(s)
- Promoter: Martinet Wim
- Co-promoter: Van Der Veken Pieter
- Fellow: Mertens Freke
Research team(s)
Project type(s)
- Research Project
Characterization and validation of novel autophagy-inducing molecules identified via high-throughput screening: a therapeutic option for the treatment of advanced atherosclerosis.
Abstract
Autophagy is a highly conserved intracellular recycling process that removes unnecessary or dysfunctional cellular components from the cytoplasm. Defective autophagy is a main feature of several human pathologies such as neurodegeneration, cancer and cardiovascular disease. Accordingly, there is strong interest in pharmacological agents that stimulate autophagy. Yet, the unequivocal validation of autophagy induction as a therapeutic strategy is currently lacking. Many obstacles remain, including the absence of potent, selective, and druglike autophagy inducers and easily transmissible preclinical results obtained with such compounds. This project aims to address the existing limitations in the field. We recently performed a phenotypic high-throughput screen on a library of diverse lead-like molecules and several novel autophagy-inducing molecules were identified. Moreover, derivatives of the initial hits were synthesized in order to obtain drug-like compounds with a more favorable biopharmaceutical profile. In this proposal, the autophagy-inducing potency and pharmacokinetic profile of the identified hits and derivatives will be thoroughly characterized both in vitro and in vivo. Moreover, the most promising autophagy inducer will be tested in a mouse model of advanced atherosclerosis. We expect that the knowledge and molecular tools generated by this project will have a major impact on (pre)clinical drug research and may improve human health through autophagy induction.Researcher(s)
- Promoter: Martinet Wim
- Fellow: Mertens Freke
Research team(s)
Project type(s)
- Research Project