Validation of new pharmacological hits for the treatment of inflammatory diseases and pain

• Grant number: 16/17773-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2016
• End date: June 30, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Thiago Mattar Cunha
• Grantee: Nerry Tatiana Cecilio
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID
• Associated scholarship(s): 17/07863-5 - Identification of pathways signaling for autophagy involved in macrophage senescence using CRISPR-Cas9 genome wide screening, BE.EP.PD

Abstract

Inflammatory diseases are a complex and heterogeneous group of diseases, which are a major cause of morbidity and mortality and an important socioeconomic problem. Despite recent scientific and technological advances, the current treatment options for inflammatory diseases are still limited and in some cases, inefficient. The mission of the Center of Research in Inflammatory Diseases (CRID) is to perform translational research, basic and clinical research in the area of inflammatory diseases. In the last years several studies in CRID labs have characterized the role of some molecules in the pathophysiology of inflammatory diseases. Based on these targets, the aim of this project is to validate the potential modulator compounds designed in silico, able to interact selectively with these targets. In this context, the present plan of activities has two main aims: 1) to clone and express the recombinant PAD4 enzyme, validate a cellular assay for the characterization of PAD4 inhibitors and test these compounds in Rheumatoid Arthritis experimental model and 2) perform screening of compounds with potential antagonist effect for the NOD2 receptor, characterize these compounds using in vitro bioassays and test these inhibitors Rheumatoid Arthritis experimental model. In addition, the last aim of this proposal will be directed to the drug development for pain treatment, another goal of our research group. For this, we will be developed of Nav1.8-overexpressing sensory neurons cell lines to characterize new potential inhibitory compounds for Nav1.8 channel, using molecules developed in partnership with the INCT-INOFAR. (AU)