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.