Structural optimization of new compounds for the treatment of fibrodysplasia ossificans progressive based on metabolism profiles acquired through metabolite identification

• Grant number: 16/07381-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 01, 2016
• End date: September 30, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Rosangela Gonçalves Peccinini
• Grantee: Elias Carvalho Padilha
• Supervisor: Xin Xu
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: National Institutes of Health, Rockville (NIH), United States
• Associated to the scholarship: 14/20833-0 - Pharmacokinetic screening and in vitro studies for the selection of new thiazolidinediones with promising oral administration capability, BP.DR

Abstract

The Laboratory of Preclinical Pharmacokinetics of New Drugs and Medicines is a research group involved in the pharmacokinetics study of new drugs in Brazil. Many new compounds are found with unfavourable pharmacokinetics characteristics despite observable pharmacologic effect. The explanation may be in the metabolites of these drugs, therefore the study of these products will improve the development of new drugs in the country. Toward this goal, the School of Pharmacy, UNESP, proposed a collaboration with the National Center for Advancing Translational Sciences (NCATS) to develop strategies using Drug Metabolism Concept in order to support the chemical structure optimization in Drug Discovery for Rare and Neglected Diseases. The target disease will be Fibrodysplasia ossificans progressiva (FOP), a rare disease with limited therapeutic alternatives. The only drug candidate, LDN-193189, demonstrated effectiveness to its treatment and presented moderate pharmacokinetics. Therefore, the joint collaboration aims to improve drug candidates for the treatment of FOP through concepts of metabolite identification (MetID), while expanding the PhD student knowledge for the discovery and development of drugs in Brazil. (AU)

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)

PADILHA, ELIAS C.; WANG, JIANYAO; KERNS, ED; LEE, ARTHUR; HUANG, WENWEI; JIANG, JIAN-KANG; MCKEW, JOHN; MUTLIB, ABDUL; PECCININI, ROSANGELA G.; YU, PAUL B.; et al. Application of in vitro Drug Metabolism Studies in Chemical Structure Optimization for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP). FRONTIERS IN PHARMACOLOGY, v. 10, APR 24 2019. (16/07381-8)