From Hit Seeking to Magic Bullets: The Successful Union of Epigenetic and Fragment Based Drug Discovery (EPIDD plus FBDD)

Author(s)

Vaidergorn, Miguel M. ^[1] ; Emery, Flavio da Silva ^[1] ; Ganesan, A. ^[2]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ East Anglia, Sch Pharm, Norwich NR4 7TJ, Norfolk - England

• Document type: Journal article
• Source: Journal of Medicinal Chemistry; v. 64, n. 19, p. 13980-14010, OCT 14 2021.
• Web of Science Citations: 0

Abstract

We review progress in the application of fragment-based drug discovery (FBDD) to epigenetic drug discovery (EPIDD) targeted at epigenetic writer and eraser enzymes as well as reader domains over the last 15 years. The greatest successes to date are in prospecting for bromodomain binding ligands. From a diverse array of fragment hits, multiple potent and selective compounds ensued, including the oncology clinical candidates mivebresib, ABBV-744, pelabresib, and PLX51107. (AU)

• FAPESP's process: 17/21146-4 - Heterocyclic chemistry and epigenetic for the development of library of compounds for medicinal chemistry purposes.
• Grantee: Flavio da Silva Emery
• Support type: Regular Research Grants
• FAPESP's process: 13/50677-7 - Exploring epigenetic targets to fight neglected diseases: Selective sirtuin-2 inhibitors as leishmanicidal compounds
• Grantee: Flavio da Silva Emery
• Support type: Research Grants - Research Partnership for Technological Innovation - PITE