DEgradation TRIggered by MOdular DEsign (DETRIMODE) is a multidisciplinary project that has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 797077 (Individual Fellowship, call H2020-MSCA-IF-2017).

The project duration is 24 months, divided in phases with different scientific targets and objectives mapped out in a detailed working plan.

The project, started in 2018, will be pursued within the Medicinal Chemistry Department of Nerviano Medical Sciences Srl, the company of the NMS Group engaged in the discovery of new small molecule drugs.  Nerviano Campus’ consolidated expertise in drug discovery and lead finding, such as its chemistry skills in solid phase synthesis methodologies will be exploited to achieve the project’s goal.

DETRIMODE main focus is the technology of targeted protein degradation, a research field that has been recently developed, immediately becoming one of the “hot areas” in chemical biology.

Targeted protein degradation represents an innovative therapeutic method that relies on a powerful technique for protein silencing, creating a novel paradigm for drug discovery.

This technology is based on Targeted Protein Degradation Inducers (TPDIs, also called PROTAC) molecules. TPDIs are heterobifunctional compounds that are able to interact with a target protein while hijacking the cellular proteosome system, responsible for the degradation of the protein itself. TPDIs are therefore capable of degrading the targeted protein, resulting in a rapid depletion of the specific protein pool.

The aim of the DETRIMODE project is the development of a methodology platform for the design and synthesis of TPDIs. The platform will mainly rely on solid phase synthetic techniques. This innovative strategy in the field of TPDIs, will require the initial investigation of the chemical reactions involved in the solid phase synthesis of intermediates, followed by the validation of the scope of reactions. This will facilitate the modular synthesis of an array of advanced synthetic intermediates to be coupled with desired target protein ligands. Once developed, the platform will allow the synthesis of targeted library of TPDIs, to be tested for their effect in cellular context.

DETRIMODE project news was published on NMS website and it was presented at high school students during the European Biotech Week in September 2018.

Link of interest:

- A special issue from "Drug Disco

very Today: Technologies" on protein degradation
- A news feature from “Nature” on TDPIs

- A brief comment on protein degradation by Derek Lowe's blog "In the pipeline"
- Marie Skłodowska-Curie Actions Individual Fellowship webpage

For any information and update of the DETRIMODE project please contact pietro.picconi@nervianoms.com

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 797077.