Wednesday, March 4, 2020

Covalent Small Molecules as Enabling Platforms for Drug Discovery

Dalton, S.E. and Campos, S.

ChemBioChem, 2020
doi: 10.1002/cbic.201900674

Covalent drugs have experienced significant renewed interest in drug discovery. This resurgence has been accompanied by a better understanding of the reactivity relationships required to engage selective covalent bonds between nucleophilic proteins and electrophilic small molecules. As a result, researchers have come to the realisation that covalent molecules could also represent useful and novel tools aimed at supporting medicinal chemistry programmes. This review surveys the increasing number of drug discovery platforms employing covalent chemistries, and highlights the utility of these techniques for identifying and characterising small molecules and biological targets.

Oncogenic KRAS G12C: Kinetic and Redox Characterization of Covalent Inhibition

Minh V. Huynh, Derek Parsonage, Tom E. Forshaw, Venkat R. Chirasani, G. Aaron Hobbs, Hanzhi Wu, Jingyun Lee, Cristina M. Furdui, Leslie B. P...