A2A receptor antagonist 4
A2A receptor antagonist 4 is an orally active A2A adenosine receptor antagonist with an IC50 of 0.8-1.8 nM and a long receptor residence time. A2A receptor antagonist 4 also exhibits antagonistic activity against A1 and A2B receptors, with IC50 values of 140 nM and 12.3-56.9 nM, respectively. A2A receptor antagonist 4 blocks A2A receptor-mediated adenosine signaling and A2B receptor-mediated adenosine signaling, and remains active under adenosine-rich conditions. A2A receptor antagonist 4 dose-dependently reduces metastatic burden in a lung metastasis model. A2A receptor antagonist 4 can be used for research related to fibrosarcoma and lung metastasis.
For research use only. We do not sell to patients.
- CAS No.: 2446776-65-2
- Formula: C25H22FN7O
- Molecular Weight:455.49
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
All Adenosine Receptor Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
rA2A 1.8 nM (IC50, Low adenosine) |
rA2A 0.8 nM (IC50, High adenosine) |
hA2B 12.3 nM (IC50, Low adenosine) |
hA2B 56.9 nM (IC50, High adenosine) |
A1 140 nM (IC50) |
In Vitro
A2A receptor antagonist 4 (Compound 45) exhibits an IC50 of 1.8 nM (low adenosine) and 0.8 nM (100 µM adenosine) against the A2A receptor in the PC-12 cell cAMP assay, maintaining sub-nanomolar to low nanomolar potency under adenosine-rich conditions[1].
A2A receptor antagonist 4 exhibits an IC50 of 12.3 nM (low adenosine) and 56.9 nM (100 µM adenosine) for the A2B receptor in HEK293 cAMPZen A2B cells, maintaining nanomolar activity under tumor microenvironment-like high adenosine conditions[1].
A2A receptor antagonist 4 exhibits an IC50 of 140 nM for the A1 receptor in Ba/F3 cells, indicating significantly lower selectivity for A1 over A2A/A2B[1].
A2A receptor antagonist 4 exhibits a receptor residence time of approximately 250 min in a radioligand dissociation assay for the human A2A receptor using [3H]ZM241385, and is a long-acting/slow-dissociating dual A2A/A2B antagonist[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
| Species | Dose | Route | T1/2 | AUC0-t | Cmax | CL | Vss | F |
|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 0.864 h | 2191 ng·h/mL | 3273 ng/mL | 0.456 L/h/kg | 0.374 L/kg | / |
| Rat[1] | 1 mg/kg | i.v. | 3.39 h | 2537 ng·h/mL | 3007 ng/mL | 0.415 L/h/kg | 1.09 L/kg | / |
| Dog[1] | 1 mg/kg | i.v. | 1.13 h | 1068 ng·h/mL | 1611 ng/mL | 0.47 L/h/kg | 0.53 L/kg | / |
| Monkey[1] | 0.5 mg/kg | i.v. | 0.71 h | 187 ng·h/mL | 403 ng/mL | 2.65 L/h/kg | 1.71 L/kg | / |
| Mice[1] | 3 mg/kg | p.o. | 1.19 h | 4399 ng·h/mL | 3023 ng/mL | / | / | 68 % |
| Rat[1] | 3 mg/kg | p.o. | 3.31 h | 5191 ng·h/mL | 600 ng/mL | / | / | 69 % |
| Dog[1] | 3 mg/kg | p.o. | 1.01 h | 2620 ng·h/mL | 1233 ng/mL | / | / | 41 % |
| Monkey[1] | 3 mg/kg | p.o. | 0.89 h | 2136 ng·h/mL | 637 ng/mL | / | / | 191 % |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female wild-type C57BL/6 mice were intravenously injected with 1 × 105 MCA205 fibrosarcoma cells to establish a MCA205 fibrosarcoma lung metastasis model[1]
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Dosage:1.5, 5 and 15 mg/kg
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Administration:Oral gavage; twice daily; 15 days
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Result:Significantly and dose-dependently reduced metastatic burden in the aggressive MCA205 pulmonary metastasis model.
Chemical Information
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CAS No. 2446776-65-2
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Molecular Weight 455.49
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Formula C25H22FN7O
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SMILES
O=C(C1=CN2C(C(N)=NC(C3=CC=C(F)C=C3)=C2C4=CN5C(C=C4)=NC=C5C)=N1)NCC6CC6
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Tail-Vein Experimental Metastasis Xenograft
Tail-vein experimental metastasis xenograft models assess the ability of injected tumor cells to survive circulation, arrest in vascular beds, extravasate, and colonize distant organs, most commonly lung after lateral tail-vein injection; this model bypasses primary-tumor formation, local invasion, and intravasation, so the readout reflects late metastatic colonization rather than the full metastatic cascade. The main readouts are metastatic burden measured by bioluminescence imaging, gross metastatic nodules, histology, organ weight, survival, or ex vivo tumor-cell quantification; luciferase-labeled tumor cells permit longitudinal noninvasive monitoring, while histology confirms organ colonization and tissue localization.
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Splenic/Portal-Vein Liver Metastasis Xenograft
Splenic and portal-vein liver metastasis xenograft models deliver tumor cells into the portal circulation so that cells reach the liver first and form hepatic metastatic lesions; splenic injection uses the spleen as an access route to the portal system, while direct portal-vein injection introduces cells into the portal vein without requiring splenectomy. The assay detects liver colonization, intrahepatic tumor growth, tumor distribution, treatment response, survival, and liver-metastasis microenvironment changes; readouts include bioluminescence or fluorescence imaging, gross liver nodule counts, liver weight or tumor burden, histology, and survival.
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Intracardiac/Intra-Arterial Metastasis Xenograft
Intracardiac xenograft metastasis models are based on the direct delivery of fluorescent or bioluminescent tumor cells into the left ventricle of immunocompromised mice, allowing systemic arterial dissemination that mimics hematogenous spread and enables colonization of distant organs such as bone, brain, and lung. Real-time bioluminescence imaging (BLI) is used to non-invasively track tumor cell seeding, survival, and metastatic outgrowth over time, reflecting early arrest in capillary beds followed by organ-specific colonization and proliferation.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
A2A receptor antagonist 4 Related Classifications
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