Tuesday, October 6, 2020

Approaches to Mitigate the Risk of Serious Adverse Reactions in Covalent Drug Design

Thomas A. Baillie (2020) Approaches to Mitigate the Risk of Serious Adverse Reactions in Covalent Drug Design, Expert Opinion on Drug Discovery 

DOI: 10.1080/17460441.2021.1832079

A review is provided of the current status of the covalent drug approach, emphasizing the unique benefits and attendant risks associated with reversible and irreversible binders. Areas of application beyond inhibition of tyrosine kinases are presented, and design considerations to de-risk covalent inhibitors with respect to undesirable off-target effects are discussed.

Acrylamide Bioisosterism: Alkenyl Aromatic Heterocycles as Reactivity-Tunable Warheads for Covalent BTK Inhibitors

Zeyue Huang, Xiuqi Hu, Zheng Liu, Hongxuan Cao, Yunjie Xiang, Jian Wan, Ivailo Slavchev, Li Rao, Ivanka Nikolova, Petar Grozdanov, Nadya Nik...