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Purity: ≥98%
Ciforadenant (formerly known as CPI-444; V-81444) is a potent, selective and orally bioactive small molecule inhibitor of the adenosine-A2a receptor (A2AR) on T-lymphocytes with anticancer and immunomodulatory activities and the potential to be used in cancer immunotherapy. Ciforadenant is presently being tested against a variety of solid tumors in a Phase I clinical trial both as a single agent and in conjunction with the PD-L1 inhibitor atezolizumab. It is possible to elicit antitumor responses with ciporadenant. When taken orally, ciporadenant binds to adenosine A2A receptors expressed on the surface of immune cells, such as DCs, T-lymphocytes, macrophages, and natural killer (NK) cells. This stops tumor-released adenosine from interacting with these important immune surveillance cells' A2A receptors, thereby reversing the immunosuppressive effects of adenosine in the tumor microenvironment.
| Targets |
A2AR ( Ki = 3.54 nM )
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| ln Vitro |
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| Enzyme Assay |
Ciforadenant (also known as CPI-444 and V81444) is a potent, selective and and orally bioactive small molecule inhibitor of the adenosine-A2a receptor (A2AR) on T-lymphocytes..
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| Cell Assay |
CPI-444 is a potent, oral, selective antagonist of A2AR. The effectiveness of CPI-444 treatment both alone and in conjunction with anti-PD-L1 is negated by CD8+ T cell depletion, suggesting a function for CD8+ T cells in mediating both primary and secondary immune responses. CPI-444±anti-PD-L1'santitumorefficacy is linked to elevated CD8+ cell infiltration and activation in MC38 tumor tissues, as well as an increase in PD-1 expression on CD8+ T cells in the spleen. Furthermore, treatment with CPI-444 modifies the levels of immune checkpoints on tumor infiltrating lymphocytes and circulating T cells, such as GITR, OX40, and LAG3. This suggests a broad role for adenosine-mediated immunosuppression.
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| Additional Infomation |
Ciforadenant is under investigation in clinical trial NCT02253745 (Safety, Tolerability, PK & Efficacy of V81444 in Volunteers With Attention Deficit/ Hyperactivity Disorder (ADHD)).
Ciforadenant is a small molecule immune checkpoint inhibitor of the adenosine A2A receptor (ADORA2A) with potential antineoplastic activity. Upon oral administration, ciforadenant binds to adenosine A2A receptors expressed on the surface of immune cells, including T-lymphocytes, natural killer (NK) cells, macrophages and dendritic cells (DCs). This prevents tumor-released adenosine from interacting with the A2A receptors on these key immune surveillance cells, thereby abrogating adenosine-induced immunosuppression in the tumor microenvironment. This may stimulate anti-tumor immune responses, resulting in tumor regression. |
| Molecular Formula |
C20H21N7O3
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| Molecular Weight |
407.43
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| Exact Mass |
407.17
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| Elemental Analysis |
C, 58.96; H, 5.20; N, 24.07; O, 11.78
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| CAS # |
1202402-40-1
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| Related CAS # |
1202402-40-1; 1202402-47-8 (R-isomer); 2102305-11-1 (racemic)
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| PubChem CID |
44537963
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| Appearance |
Solid powder
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| LogP |
0.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
573
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CC=C(O1)C2=C3C(=NC(=N2)N)N(N=N3)CC4=NC(=CC=C4)CO[C@H]5CCOC5
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| InChi Key |
KURQKNMKCGYWRJ-HNNXBMFYSA-N
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| InChi Code |
InChI=1S/C20H21N7O3/c1-12-5-6-16(30-12)17-18-19(24-20(21)23-17)27(26-25-18)9-13-3-2-4-14(22-13)10-29-15-7-8-28-11-15/h2-6,15H,7-11H2,1H3,(H2,21,23,24)/t15-/m0/s1
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| Chemical Name |
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (5.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4544 mL | 12.2720 mL | 24.5441 mL | |
| 5 mM | 0.4909 mL | 2.4544 mL | 4.9088 mL | |
| 10 mM | 0.2454 mL | 1.2272 mL | 2.4544 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05501054 | Recruiting | Drug: Ipilimumab Drug: Nivolumab Drug: Ciforadenant |
Renal Cell Carcinoma | M.D. Anderson Cancer Center | February 9, 2023 | Phase 1 Phase 2 |
| NCT04280328 | Completed | Drug: Ciforadenant Drug: daratumumab |
Multiple Myeloma | Corvus Pharmaceuticals, Inc. | February 20, 2020 | Phase 1 |
| NCT03454451 | Completed | Drug: CPI-006 Drug: CPI-006 + ciforadenant |
Sarcoma Bladder Cancer Cervical Cancer Ovarian Cancer |
Corvus Pharmaceuticals, Inc. | April 25, 2018 | Phase 1 |
| NCT02655822 | Completed | Drug: Ciforadenant Drug: Ciforadenant + atezolizumab |
Renal Cell Cancer Metastatic Castration Resistant Prostate Cancer |
Corvus Pharmaceuticals, Inc. | January 2016 | Phase 1 |
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