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Updated: Oct 15, 2025

A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
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Structural analysis and binding sites of inhibitors targeting the CD47/SIRPα interaction in anticancer therapy

Bo Huang1, Zhaoshi Bai2, Xinyue Ye3

  • 1Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, Jiangsu 211198, China.

Computational and Structural Biotechnology Journal
|October 29, 2021
PubMed

Insights

Small molecules targeting the CD47/SIRPα pathway offer a promising alternative to large biomolecules for cancer immunotherapy, with improved drug properties. Computer-aided drug discovery aids in developing these novel small-molecule inhibitors.

Area of Science:

  • Immunology
  • Pharmacology
  • Structural Biology

Background:

  • The CD47/SIRPα pathway is a key innate immune checkpoint, inhibiting immune surveillance and clearance of cancer cells.
  • Blocking this pathway demonstrates significant anti-tumor effects in clinical trials, making it a target for cancer immunotherapy.
  • Current CD47/SIRPα inhibitors in trials are biomacromolecules with limitations in permeability and oral bioavailability.

Purpose of the Study:

  • To review recent advancements in understanding CD47/SIRPα interactions.
  • To summarize small-molecule inhibitors targeting the CD47/SIRPα pathway.
  • To analyze crystal structures and CADD data to guide future inhibitor development.

Main Methods:

  • Literature review of CD47/SIRPα interactions, peptides, and small molecule inhibitors.
  • Computer-aided drug discovery (CADD) analysis of published crystal structures.
  • Docking simulations of small molecule inhibitors against CD47/SIRPα.

Main Results:

  • Biomacromolecules are currently the primary CD47/SIRPα inhibitors in clinical trials.
  • Small-molecule inhibitors are being developed to overcome limitations of biomacromolecules.
  • CADD analysis provides insights into key interactions for small molecule inhibitor design.

Conclusions:

  • Small-molecule inhibitors represent a promising avenue for CD47/SIRPα-targeted cancer immunotherapy.
  • Understanding structural interactions is crucial for designing effective small-molecule inhibitors.
  • CADD approaches can accelerate the development of novel CD47/SIRPα inhibitors with improved pharmacokinetic properties.
Keywords:
CD47/SIRPαComputer-aided drug discoveryCrystal structureHot spotImmunotherapyInhibitor

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