Macrocyclic compounds as strategy for kinase-related chemical probe development

• Grant number: 18/22363-1
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2019
• End date: February 28, 2021
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Agreement: University of Toronto
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Katlin Brauer Massirer
• Grantee: Katlin Brauer Massirer
• Principal researcher abroad: Andrei Yudin
• Institution abroad: University of Toronto (U of T), Canada
• Host Institution: Centro de Biologia Molecular e Engenharia Genética (CBMEG). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 14/50897-0 - INCT 2014: Open-acess Medicinal Chemistry Centre (OpenMedChem), AP.TEM

Abstract

Recent advances have highlighted the advantages of using macrocyclic compounds as a basis for protein kinase inhibitors. However, the design and synthesis methodologies for such macrocyclic inhibitors are at an early stage. SGC-Unicamp works on inhibitor development for several protein kinases which are good candidates for development of macrocyclic inhibitors. Those candidate kinases can bind inhibitors with small hinge-binding groups and sometimes, can also accommodate ligands in a teardrop binding mode. Additionally, new macrocyclic compounds can be screened against the SGC-Unicamp in-house panel of 40+ human protein kinases to identify new opportunities for inhibitor development. Whenever possible, SGC-Unicamp will perform co-crystallization trials and solve co-crystal structures for the target proteins in complex with the macrocyclic inhibitors. (AU)