inhibitAUTO · Towards a New Frontier in Autophagy Inhibition: The Development of a Novel Class of Chemical Probes and Identification of Their Associated Biological Target
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-03-01 → 2020-02-29
- EU contribution
- €171,461
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Towards a New Frontier in Autophagy Inhibition: The Development of a Novel Class of ChemicalProbes and Identification of Their Associated Biological Target
The dysregulation of the lysosomal degradation (autophagy) pathway has been implicated in several degenerative conditions including cancer. The development of efficient measures to control autophagy therefore potentially offers a desperately needed pathway through which cancer progression may be regulated. Around a quarter of deaths in Europe are currently attributed to cancer, and it is estimated that 90% of these deaths are caused by metastases. Inhibition of autophagy has recently been shown to block cell migration and prevent metastases in tumour models. This action aims to discover a novel class of autophagy inhibitors and newly develop chemical probes that can identify their protein targets, and dissect their biological mode of action in relation to autophagy modulation.
Data: CORDIS, © European Union
Project objective
This action aims to discover a novel class of autophagy inhibitors and newly develop chemical probes that can identify theirprotein targets and dissect their biological mode of action. Autophagy dysregulation is intrinsically linked with majorEuropean healthcare challenges, including cancer. The identification of new classes of druggable autophagic proteins willhave broad implications for the development of novel and more effective cancer therapeutics. To address the aims of thisaction, this proposal seeks support to initiate a pioneering and holistic chemical biology programme, which combines thenewest technologies in synthetic chemistry and cell biology. Phenotypic investigations in the host lab recently identified newinhibitors of autophagy based on a novel scaffold, which modulates autophagy through an exciting but unknown pathway. Inthis action the use of a newly introduced sp2-sp3 cross-coupling reaction will allow systematic variation of the scaffold,exploration of its structure-activity relationship, and improvement of the potency of these inhibitors to facilitate thepreparation of high-quality chemical probes. A focused compound collection (>100 compounds) will be prepared andinvestigated in cell-based assays, with the aim of establishing a broad, potent and selective class of inhibitors. The inhibitorymode of action will then be rationalised through identification, validation and engagement of the associated biological targetsusing further cell-based investigations and biophysical assays. Chemical probes will be generated from the most activeinhibitors and used to identify and interrogate the druggability of a novel protein target with potentially huge significance forbiomedical science. My ambition is to become an independent academic researcher in chemical biology at a leadingEuropean institution, and this Fellowship provides a vital opportunity for me to advance my scientific and career potential.
Original text from CORDIS.
Participants
- MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV · MUNCHENCoordinatorGermany
Links
- View on CORDIS
- DOI: 10.3030/794259
- http://www.mpi-dortmund.mpg.de/institute/directors/herbert-waldmann
Data: CORDIS, © European Union