Imaradenant | A2AR antagonist

Imaradenant chemical structure

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Imaradenant (1321514-06-0) is a potent and selective A2AR antagonist (IC50 = 0.79 nM @ 0.1 µM adenosine).1  It restores T cell function and tumor antigen cross-presentation by CD103+ dendritic cells resulting in enhanced antitumor immunity. Imaradenant reduced tumor load in a murine model of multiple myeloma in combination with anti-CD73 therapy.2 It displayed efficacy in combination with PD-1 inhibitors against prostate cancer.3,4 AZD4635 increased the infiltration of cytotoxic T cells and decreased infiltration of immunosuppressive cells to increase the efficacy of PARP inhibitors in an ovarian cancer model.5

References/Citations:

  1. Borodovsky et al. (2020), Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity; J. Immunol. Cancer 8 e000417
  2. Yand et al. (2020), Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade; J. Immunol. Cancer 8 e000610
  3. Lim et al. (2022), Phase 1a/b. Open-Label, Multicenter Study of AZD4635 (an Adenosine A2A Receptor Antagonist) as Monotherpay or Combined with Durvalumab, in Patients with Solid Tumors; Clin. Cancer Res. 28 4871
  4. Falchook et al. (2024), A phase 2 study of AZD4635 on combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer; Cancer Immunol. Immunother. 73 72
  5. Pan et al. (2026), AZD4635 Targets cAMP/CREB Axis to Salvage PARPi-Induced Immune Evasion and Enhance Antitumor Efficacy in Ovarian Cancer; Pharmaceutics 18 257
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Alternate Name:
AZD4635

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Imaradenant (1321514-06-0) is a potent and selective A2AR antagonist (IC50 = 0.79 nM @ 0.1 µM adenosine).1  It restores T cell function and tumor antigen cross-presentation by CD103+ dendritic cells resulting in enhanced antitumor immunity. Imaradenant reduced tumor load in a murine model of multiple myeloma in combination with anti-CD73 therapy.2 It displayed efficacy in combination with PD-1 inhibitors against prostate cancer.3,4 AZD4635 increased the infiltration of cytotoxic T cells and decreased infiltration of immunosuppressive cells to increase the efficacy of PARP inhibitors in an ovarian cancer model.5

References/Citations:

  1. Borodovsky et al. (2020), Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD103+ dendritic cells enhancing anti-tumor immunity; J. Immunol. Cancer 8 e000417
  2. Yand et al. (2020), Conversion of ATP to adenosine by CD39 and CD73 in multiple myeloma can be successfully targeted together with adenosine receptor A2A blockade; J. Immunol. Cancer 8 e000610
  3. Lim et al. (2022), Phase 1a/b. Open-Label, Multicenter Study of AZD4635 (an Adenosine A2A Receptor Antagonist) as Monotherpay or Combined with Durvalumab, in Patients with Solid Tumors; Clin. Cancer Res. 28 4871
  4. Falchook et al. (2024), A phase 2 study of AZD4635 on combination with durvalumab or oleclumab in patients with metastatic castration-resistant prostate cancer; Cancer Immunol. Immunother. 73 72
  5. Pan et al. (2026), AZD4635 Targets cAMP/CREB Axis to Salvage PARPi-Induced Immune Evasion and Enhance Antitumor Efficacy in Ovarian Cancer; Pharmaceutics 18 257