USP2-TD · Revolving around the ubiquitin‒proteasome system: USP2-targeted degrader
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2021-10-01 → 2023-09-30
- Финансиране от ЕС
- 212 934 €
- Участници
- 1
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Протеинът USP2 и начинът за неговото разграждане чрез технология, наречена PROTAC, са в центъра на работата. Разбирането на функциите на този протеин помага при търсенето на нови методи за лечение на различни видове рак.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Revolving around the ubiquitin‒proteasome system: USP2-targeted degrader
This project deals with the discovery of an appropriate chemical tool that allows the study of a protein. This protein is called ubiquitin-specific protease 2 (USP2) and belongs the superfamily of deubiquitinating enzymes (DUBs). While USP2 has been associated with a wide variety of cancers and represents a very promising therapeutic target, it still requires to be validated for its therapeutic potential. In that context, having an appropriate chemical tool would allow a confident interrogation and further understanding of USP2 biology and disease. This tool can likewise serve as starting point and eventually feed drug discovery projects for USP2-targeted treatments. To this end, an innovative approach endowed with great potential has recently emerge. This technology is called proteolysis-targeting chimera (PROTAC) and consists of pursuing the degradation of a protein that is upregulated, thereby evoking a certain disease. Herein, we aimed at the development of an USP2-targeted degrader (USP2-TD) based on PROTAC technology. This research has been carried out in the Spring group at the University of Cambridge and involved a 6-month placement in the Ciulli group at the University of Dundee. At the time of the end of the action, the project is still ongoing. Preliminary data showed two major findings: - We identified a candidate with the potential to become an USP2-TD. - We discovered a natural interaction between USP2 and an unrelated complex of proteins. Given these promising results, these projects will be investigated in a collaboration between the Universities of Barcelona, Cambridge, and Dundee. Success in these studies can lead to major advances in the knowledge and treatment of USP2-related diseases.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Targeting DUB enzymes has recently emerged as a promising opportunity for drug discovery that might lead to more selective, less toxic drug profiles. Target validation of these enzymes is currently a priority in the field, as we are lacking of appropriate chemical probes for most of them. A clear example is USP2, whose chemical inhibition has been barely explored, leading to a poor-quality chemical probe that has been extensively used by biologist during the last decade. Hence, this multidisciplinary project emerges to address the identified unmet need of providing the scientific community with an appropriate chemical probe for a confident interrogation and further understanding of USP2 biology and disease. This probe will be useful for a suitable validation of this promising target and can eventually feed drug discovery projects for USP2-related cancer treatments.Herein, we aim to develop a, USP2-Targeted Degrader (USP2-TD) that overcomes the lack of selectivity and potency of its parent counterpart. This small-molecule USP2-TD will enable investigations of selective USP2 downregulation with exquisite quantitative and temporal control of protein levels. To this end, the proposed research deal with the identification of solvent-exposed region at the parent, the discovery of the USP2-TD, and its validation as chemical probe for USP2.
Оригинален текст от CORDIS (на английски).
Участници
- THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGEКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз