From Hit Seeking to Magic Bullets: The Successful Union of Epigenetic and Fragment Based Drug Discovery (EPIDD + FBDD)
Miguel de Menezes Vaidergorn, Flávio da Silva Emery, A. Ganesan
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.
Topics & Concepts
EpigeneticsDrug discoveryFragment (logic)ChemistryBromodomainComputational biologyPharmacologyMedicineBiochemistryBiologyComputer scienceGeneAlgorithmProtein Degradation and InhibitorsHistone Deacetylase Inhibitors ResearchMultiple Myeloma Research and Treatments