Covalent Inhibition in Drug Discovery. Academic Article uri icon

abstract

  • Although covalent inhibitors have been used as therapeutics for more than a century, there has been general resistance in the pharmaceutical industry against their further development due to safety concerns. This inclination has recently been reverted after the development of a wide variety of covalent inhibitors to address human health conditions along with the US Food and Drug Administration (FDA) approval of several covalent therapeutics for use in humans. Along with this exciting resurrection of an old drug discovery concept, this review surveys enzymes that can be targeted by covalent inhibitors for the treatment of human diseases. We focus on protein kinases, RAS proteins, and a few other enzymes that have been studied extensively as targets for covalent inhibition, with the aim to address challenges in designing effective covalent drugs and to provide suggestions in the area that have yet to be explored.

published proceedings

  • ChemMedChem

altmetric score

  • 28.68

author list (cited authors)

  • Ghosh, A. K., Samanta, I., Mondal, A., & Liu, W. R.

citation count

  • 130

complete list of authors

  • Ghosh, Avick Kumar||Samanta, Indranil||Mondal, Anushree||Liu, Wenshe Ray

publication date

  • May 2019

publisher