RRx-001, a downregulator of the CD47- SIRPα checkpoint pathway, does not cause anemia or thrombocytopenia

Expert Opin Drug Metab Toxicol. 2021 Apr;17(4):355-357. doi: 10.1080/17425255.2021.1876025. Epub 2021 Jan 22.


Introduction: The CD47 and SIRPα checkpoint pathway has garnered much interest within the anti-cancer research community, with multiple experimental checkpoint inhibitors targeting CD47 and SIRPα in development. The use of such checkpoint inhibitors may however be limited by hematologic toxicity.Areas covered: We report on RRx-001, the first known small molecule downregulator of CD47 and SIRPα, which has shown a lack of hematologic toxicity in clinical trials.Expert opinion: RRx-001 is the first reported small molecule downregulator of CD47 and SIRPα and lacks any notable hematologic or systemic toxicity as demonstrated in clinical trials to date. Small molecule RRx-001 could be used in combination with or in place of CD47 targeting antibodies for anti-cancer treatment.

Keywords: CD47; Oncology; PPAR-γ; SIRPα; antibody; checkpoint inhibitor; immunotherapy; small molecule.

MeSH terms

  • Anemia / epidemiology
  • Anemia / etiology
  • Antigens, Differentiation / metabolism
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacology
  • Azetidines / administration & dosage
  • Azetidines / adverse effects*
  • Azetidines / pharmacology
  • CD47 Antigen / metabolism
  • Humans
  • Nitro Compounds / administration & dosage
  • Nitro Compounds / adverse effects*
  • Nitro Compounds / pharmacology
  • Receptors, Immunologic / metabolism
  • Thrombocytopenia / epidemiology
  • Thrombocytopenia / etiology


  • Antigens, Differentiation
  • Antineoplastic Agents
  • Azetidines
  • CD47 Antigen
  • CD47 protein, human
  • Nitro Compounds
  • RRx-001
  • Receptors, Immunologic
  • SIRPA protein, human