TRPV1-targeted ligand-drug conjugates to treat prostate cancer

Información del proyecto

TRPLigDrugConj

Identificador del acuerdo de subvención: 743640

DOI

10.3030/743640

Proyecto cerrado

Fecha de la firma de la CE 15 Febrero 2017

Fecha de inicio 1 Marzo 2017

Fecha de finalización 4 Mayo 2019

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 160 635,60

Aportación de la UE

€ 160 635,60

Coordinado por

INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Portugal

Periodic Reporting for period 1 - TRPLigDrugConj (TRPV1-targeted ligand-drug conjugates to treat prostate cancer)

Período documentado: 2017-03-01 hasta 2019-02-28

Resumen del contexto y de los objetivos generales del proyecto

Cancer remains a global health threat, in some cases, with limited therapies available. Prostate cancer is one of the most prevalent cancer types in male individuals and new, selective medications, ideally with new modes of action are urgently sought after. In this project we explore both a new mechanism of action and chemical entities to treat prostate cancer. The project tackles a major societal challenge and aims at validating a therapeutic strategy for future development.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

The project is comprised of several tasks that build on each other towards the end goal, as described below:
1) validation of the drug target in prostate cancer. A range of chemical and bioinformatics techniques were employed to assert the importance of the studied drug target. In particular we found that the target is not only relevant for personalized medicines, but can serve as a marker for diagnostic of prostate cancer;
2) design and synthesis of small molecules that bind to the studied drug target. The task equally involved the biochemical profiling of all synthesized chemical entities.
3) synthesis of chemical imaging probes to study the dynamics of the studied drug target. The task involved in vitro chemical reaction for optical imaging and tracking of the dynamics via microscopy.
4) design and synthesis of conjugate systems targeting the protein under study. The task involved not only the synthesis of conjugate molecules, but also the study of their stability under simulated physiological conditions.
5) In vitro profiling of the synthesized conjugate molecules, in a prostate cancer cell line.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

The project exploits a new paradigm in molecular medicine, by conjugating a ligand molecule and cytotoxic agent. This way, a new entity is obtained that will selectively target diseased cells. Using this approach one can not only mask the cytotoxic effects of the therapy, but also ascertain an effective concentration of the therapeutics at the tumor site. Altogether, the strategy is expected to increase treatment efficiency in patients over expressing the drug target under study. Also, the strategy exploits a new mechanism of action, that has been proven selective for cancer and thereby reducing potential side effects exerted by the cytotoxic agent.

Summary of strategy