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Updated: Sep 22, 2025

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
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Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

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Small Molecule Agents Targeting PD-1 Checkpoint Pathway for Cancer Immunotherapy: Mechanisms of Action and Other

Pottayil G Sasikumar1, Murali Ramachandra1

  • 1Aurigene Discovery Technologies Limited, Bangalore, India.

Frontiers in Immunology
|May 19, 2022
PubMed

Insights

Small molecule inhibitors targeting the programmed cell death protein 1 (PD-1) pathway offer new avenues for cancer immunotherapy. This review explores their development, mechanisms, and clinical potential beyond antibody therapies.

Area of Science:

  • Oncology
  • Immunology
  • Medicinal Chemistry

Background:

  • Antibodies targeting immune checkpoints like PD-1 and CTLA-4 have revolutionized cancer therapy.
  • Limitations of antibody-based treatments include low response rates and immune-related adverse events.
  • Novel strategies, including small molecule inhibitors, are crucial for advancing cancer immunotherapy.

Purpose of the Study:

  • To review small molecule agents targeting the PD-1 checkpoint pathway for cancer immunotherapy.
  • To highlight diverse chemotypes, their characterization (binding, functionality), and mechanisms of action.
  • To discuss learnings from clinical trials and considerations for future development.

Main Methods:

  • Literature review of small molecule checkpoint inhibitors targeting PD-1.
  • Analysis of reported chemotypes, scaffolds, binding affinities, and functional assays.
  • Examination of published mechanisms of action and clinical trial data.

Main Results:

  • Identification of various small molecule chemotypes/scaffolds targeting the PD-1 pathway.
  • Characterization of their binding and functional properties.
  • Overview of their mechanisms and early clinical development insights.

Conclusions:

  • Small molecule PD-1 inhibitors represent a promising alternative/adjunct to antibody therapies.
  • Further research and clinical development are needed to optimize their efficacy and safety.
  • These agents hold potential for improving cancer immunotherapy outcomes.
Keywords:
PD-L1 inhibitorscancer immunotherapymechanism of action (MOA)small molecule PD-1/PD-L1 inhibitorssmall molecule immunomodulators

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