Design and synthesis of small molecules targeting transcription factors NPAS1 and NPAS3

• Grant number: 22/00759-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 31, 2022
• End date: August 30, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Ronaldo Aloise Pilli
• Grantee: Ian de Toledo
• Supervisor: Paul E. Brennan
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Oxford, England
• Associated to the scholarship: 19/25008-0 - Design and synthesis of STK10 and VRK2 kinase inhibitors, BP.DR

Abstract

Neuropsychiatric disorders are a relatively common but very debilitating condition and encompasses conditions such as schizophrenia, bipolar disorders and major depressive disorders. They have a high degree of heritability which can be linked to genetic abnormities in the genetic transcription of the DNA information. The regulatory transcription factors are a very important class of protein which regulates the transcription process. The NPAS1 and NPAS3 transcription factors are a member of the subfamily bLHL-PAS and their dysregulation have been shown to be linked to many neuropsychiatric disorders. In this project we aim to discover first-in-class small molecules which will help us to elucidate their importance in the context of the neuropsychiatric disorders. In order to achieve this goal, we will screen a large compound libraries employing HTS (high-throughput screening) and VLS (virtual library screening) to find hits which will be further elaborated into potent small molecules through structural optimization both in enzymatic and cellular context. These potent small molecules will then be used as tools to interrogate the transcription factor function. (AU)