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DEVELOPMENT OF A NOVEL ALLOSTERIC CD73 INHIBITOR AND PET TRACER.

Grant number: 23/16292-2
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): February 29, 2024
Effective date (End): February 27, 2025
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal Investigator:Giuliano Cesar Clososki
Grantee:Victor Hugo Catricala Fernandes
Supervisor: Anna Junker
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: Eberhard Karls Universität Tübingen, Germany  
Associated to the scholarship:22/06051-5 - Rational design and synthesis of new indolizines of synthetic and medicinal interest, BP.DR

Abstract

In light of the ongoing public health challenge posed by cancer, there is a continuous need to explore novel approaches for treating and diagnosis of different cancer types. Of particular interest in our research is CD73, an enzyme that is often overexpressed in cancer tissues . Our research proposal focuses on exploring ligands designed to inhibit CD73's functionality, addressing the allosteric binding sites of the enzyme. This dual-purpose approach aims to develop therapeutic inhibitors while also considering the potential for these compounds to serve as diagnostic tools for cancer through PET imaging. A virtual fragment screening, which emerged from a collaborative effort, has led to identifying potential CD73 inhibitors; these compounds will be synthesized and subsequently evaluated. In addition to this, our proposal includes the synthesis and radioisotope labeling of a series of CD73 inhibitors employing 18F to be employed as tracers for PET imaging. Therefore, the project aims to advance the frontier of knowledge relevant to cancer diagnosis and treatment. In line with the objectives of the FAPESP BEPE program, the knowledge and skills acquired in the field of medicinal chemistry through this study will have a direct and positive influence on the ongoing PhD project in Brazil. Thus, indolizines will be further investigated as substrates for antiproliferative target assays within the established platform. Additionally, the core structure of indolizines has the potential to serve as a PET tracer if it proves effective in inhibiting CD73 and other significant biological targets, thus broadening the potential applications of this fascinating compound class.

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