„Development and implementation of an innovative platform for screening analysis of therapeutic degron-type compounds”
Project supported by the National Centre for Research and Development under the Smart Growth Operational Programme 2014-2020
PRIORITY AXIS IV: INCREASING THE RESEARCH POTENTIAL
MEASURE 4.1: Research and development
SUB-MEASURE 4.1.4: „Application projects”
Total cost: 4 968 788,76 PLN (including own contribution: 708 786,00 PLN)
EU Contribution: 2 018 633,76 PLN
Duration: 01/03/2017 – 28/02/2020
Principal Investigator: dr hab. inż. Jakub Siednienko
- Wrocławskie Centrum Badań EIT+ Sp. z o.o.– Consortium Leader
- Captor Therapeutics Sp. z o.o.
The drug discovery market is characterized by high investment rate and constant development towards innovative technologies and mechanisms. One of new fields within this scope is degradation of specific proteins in the cell induced by low molecular weight compounds (called degrons), whose therapeutic potential cannot be overestimated. The application of drugs based on degron-like compounds brings major advantage over classic therapies. The most substantial fact is that their efficiency is not dependent on the enzymatic or binding function of the target protein, which enables identification of new therapeutic targets, approaching which was not possible until recently (“undruggable proteome”, estimated to cover even 80% of human proteome). Degrons can be used towards both endogenic (e.g. cancer-involved proteins, amyloids) or exogenic proteins (e.g. virus proteins). A crucial problem which limits the induced protein degradation technology development based on degrons is a lack of quick, efficient and high-throughput assays enabling the detection of compounds which exhibit preferred activity.
The applicants challenge this issue by proposing an innovative DegScreen technology – a two-step high-throughput screening of low molecular weight compounds which induce the degradation of protein target. The technology will be implemented in the market as a service which enables screening for compounds active towards a chosen protein to be used as potential drug precursors, auxiliary compounds for determination of protein function or their role in pathogenic processes, and for assessment of the drug candidates polipharmacological profile. DegScreen will also comprise the use of an innovative optimized biased chemical compounds library with special purpose (developed by Captor Therapeutics), whose parameters are selected to bias the library towards higher potential of induced protein degradation in cells.