In vitro and in vivo validation of new pharmacology HITs for the treatment of inflammatory diseases and neuropathic pain

• Grant number: 23/08211-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2023
• End date: July 31, 2025
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Fernando de Queiroz Cunha
• Grantee: Paulo Sérgio de Almeida Augusto
• 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

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 pharmacological targets, and in collaboration with researchers from the National Bioscience Laboratory (LNBIO-CNPEM), in the last years, we have carried out new drug discovery campaigns based on large-scale assays (HTS) for different enzymatic targets. These screens and subsequent orthogonal analyzes yielded several molecules that require subsequent analyses both in vitro and in vivo for validation of the efficacy. Thus, the present project aims to validate the modulator potential of these selected compounds capable of selectively interacting with some of these targets, both in in vitro models (inflammatory cells) and in vivo (models of inflammatory diseases). In this context, the present activity plan has two objectives: 1) Evaluate the effectiveness of these inhibitors in in vitro cells models specific for the selected target and 2) Carry out proof-of-concept experiments in models of inflammatory diseases in which the selected pharmacological target has been shown to play a role crucial. (AU)