TRPV1-targeted ligand-drug conjugates to treat prostate cancer

Projektinformationen

TRPLigDrugConj

ID Finanzhilfevereinbarung: 743640

DOI

10.3030/743640

Projekt abgeschlossen

EK-Unterschriftsdatum 15 Februar 2017

Startdatum 1 März 2017

Enddatum 4 Mai 2019

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten

€ 160 635,60

EU-Beitrag

€ 160 635,60

Koordiniert durch

INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Portugal

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

Berichtszeitraum: 2017-03-01 bis 2019-02-28

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

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.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

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.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

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