Novel Atg4B inhibitors and dual Atg4B carbonic anhydrase inhibitors for interf...
Novel Atg4B inhibitors and dual Atg4B carbonic anhydrase inhibitors for interfering with cytoprotective mechanisms of cancer cells in the acidic tumor micro environment.
The microenvironment of most solid tumors tends to be significantly more acidic than healthy tissue. Inadequate perfusion, oxygen limitation and cell metabolic changes, are key causative factors for this situation. The acidic pH i...
ver más
30/04/2019
UANTWERPEN
161K€
Presupuesto del proyecto: 161K€
Líder del proyecto
UNIVERSITEIT ANTWERPEN
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Fecha límite participación
Sin fecha límite de participación.
¿Tienes un proyecto y buscas un partner? Gracias a nuestro motor inteligente podemos recomendarte los mejores socios y ponerte en contacto con ellos. Te lo explicamos en este video
Información proyecto ONCOPHAGY
Duración del proyecto: 25 meses
Fecha Inicio: 2017-03-17
Fecha Fin: 2019-04-30
Líder del proyecto
UNIVERSITEIT ANTWERPEN
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Presupuesto del proyecto
161K€
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
The microenvironment of most solid tumors tends to be significantly more acidic than healthy tissue. Inadequate perfusion, oxygen limitation and cell metabolic changes, are key causative factors for this situation. The acidic pH induces a number of specific genetic, transcriptional and metabolic effects in tumor cells. These are required for survival under increased H+-stress. Evidence is now mounting that these effects also play a major role in tumor progression, invasiveness and the development of multi-resistance to therapy. Two pivotal adaptations related to maintaining intracellular pH homeostasis in an acidic environment, have recently received significant attention: (1) the presence of chronic autophagy in tumors and (2) the overexpression of carbonic anhydrases (CAs), mainly CA IX and CA XII.
This project will biopharmaceutically optimize a novel class of specific autophagy inhibitors that target Atg4B. The specific goal of this part of the project is to obtain orally bioavailable and metabolically stable compounds that are fit for in vivo applications. The relevance of these compounds is clear, given the unmet demand for reliable, specific inhibitors in the domain of autophagy. At the same time, the project will evaluate the potential for therapy development of the compounds in the framework of cancer. Finally, the proposal will explore whether a further increase of anti-tumor efficiency can be obtained by combining Atg4B- and CA-inhibitor pharmacophores in a single compound.