Pharmacokinetic and Biological Properties Evaluation of Drug Candidates

• Grant number: 19/06034-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2019
• End date: April 30, 2021
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Adriano Defini Andricopulo
• Grantee: Julia Medeiros Souza
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

Pharmacokinetics (PK) is the study of the time course of drug absorption, distribution, metabolism and excretion (ADME), and how these ADME processes are related to the intensity and time course of the pharmacological (therapeutic and toxic) effects of drugs. Orally delivered pharmacologically active compounds must have favorable absorption and clearance properties and satisfactory metabolic stability to provide adequate systemic exposure to elicit a pharmacodynamic response. If the compounds possess reasonable physicochemical properties, have low to intermediate clearance and reasonable absorption, adequate oral bioavailability may be achieved. Because conducting an in vivo experiment is time-consuming and material-consuming, early discovery efforts have focused on assessing in vitro absorption potential and in vitro metabolic stability. Such experiments are intended to screen compounds and identify candidates that are most likely to have adequate PK properties for further pharmacological evaluation. Modifications of the in vitro and in situ approaches to assess the potential of absorption and metabolism have enabled a higher throughput and an ability to correlate better with in vivo pharmacokinetics of compounds. We have established a strong joint initiative with Drug for Neglected Diseases Initiative (DNDi) and AbbVie. In this partnership, we will evaluate both pharmacokinetic and biological properties of drug candidates. The methods employ will follow the DNDi and AbbVie pipeline for new drugs against parasitic diseases.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VALLI, MARILIA; SOUZA, JULIA MEDEIROS; CHELUCCI, RAFAEL CONSOLIN; BIASETTO, CAROLINA RABAL; ARAUJO, ANGELA REGINA; BOLZANI, VANDERLAN DA SILVA; ANDRICOPULO, ADRIANO DEFINI. Identification of natural cytochalasins as leads for neglected tropical diseases drug discovery. PLoS One, v. 17, n. 10, p. 13-pg., 2022-10-03. (19/06034-0, 13/07600-3, 14/50926-0, 19/05967-3)