Advances in cancer immunotherapy using small-molecular inhibitors targeting the PD-1/PD-L1 interaction

Area of Science:

• Oncology
• Immunology
• Medicinal Chemistry

Background:

• Cancer immune evasion involves the PD-1/PD-L1 pathway.
• Monoclonal antibodies targeting PD-1/PD-L1 have clinical success but face challenges like cost and tumor penetration.
• Small-molecule inhibitors present a promising alternative with improved characteristics.

Purpose of the Study:

• To review advancements in small-molecule inhibitors of the PD-1/PD-L1 pathway.
• To analyze their mechanisms, structural designs, and therapeutic potential in cancer treatment.
• To provide insights into the design logic and future directions for these inhibitors.

Main Methods:

• Systematic classification of various molecular structures of small-molecule PD-1/PD-L1 inhibitors.
• Analysis of relevant industrial cases and recent research findings.
• Integration of drug chemistry principles with clinical needs.

Main Results:

• Key innovations include biphenyl scaffolds and heterocyclic frameworks enhancing binding efficiency and immune activation.
• Small molecules offer improved tumor penetration and cost-effectiveness compared to antibodies.
• The review systematically categorizes structures and discusses design strategies.

Conclusions:

• Small-molecule PD-1/PD-L1 inhibitors represent a significant advancement in cancer immunotherapy.
• Their design and development offer a viable strategy to overcome limitations of current antibody-based therapies.
• Continued innovation in this area holds promise for more effective and accessible cancer treatments.