The drug discovery of converting antibody to small molecule drug (PD-L1 inhibitor)

Abstract

Blocking the immune checkpoint receptor (PD-1) or its ligand (PD-L1) with antibodies has proven to be an effective treatment for multiple cancer types, and the success of this cancer immunotherapy has led to a paradigm shift in cancer treatment. The drug discovery aimed at inhibiting the target proteins, whose pharmacological outcomes are proven to be effective with the antibody, with inexpensive and orally available small-molecule drugs has a high hurdle to overcome, but are of great significance. In this article, we will introduce various approaches to drug discovery that are unique to small molecules, which demonstrate a different mechanism of action from those of antibodies and have similar drug effects to those of antibodies.