Covalent drug discovery exploiting the new warheads

Covalent drug forms a covalent bond with desease-related target proteins irreversibly inhibits their function. In order to develop a safe and non-toxic covalent drug, it is important to device new reaction chemistry that realizes a sufficient reactivity and high target selectivity for targeted protein under the complicated biological systems such as our body. Currently, new reaction chemistry is being actively developed all over the world to achieve excellent target selectivity of covalent drugs. In this essay, we intoroduce α-chlorofluoroacetamide and bicyclobutane amide as the new reactive groups for proteineous cysteine of targeted protein and their application to develop targeted covalent inhibitors for the treatment of cancer and infecsious deseases.