Progress in the Research and Development of Biphenyl Small Molecules Targeting PD-1/PD-L1 as Potential Antitumor Drug Candidates.

Cancer remains a major global health challenge, and cancer immunotherapy has emerged as a promising treatment strategy. A key immune checkpoint in this approach is the interaction between PD-1 and PD-L1, which suppresses immune responses against tumor cells. Although monoclonal antibodies targeting PD-1/PD-L1 have shown significant therapeutic potential, their use is hampered by limitations such as high costs, extended half-lives, and the potential for immune-related side effects. In response to these challenges, there is growing interest in the development of small-molecule inhibitors that can disrupt the PD-1/PD-L1 interaction more efficiently and cost-effectively. This review focuses on the design of biphenyl-based small molecules as inhibitors of the PD-1/PD-L1 pathway. We explore various design strategies, key structural features, and recent advancements in biphenyl-derived compounds. These insights contribute to the ongoing effort to develop alternative antitumor therapies with improved pharmacological profiles and therapeutic efficacy.