ASP5854
ASP5854 is an orally active, blood-brain barrier permeable adenosine A1/A2a dual receptor antagonist. ASP5854 blocks receptor activity and agonist-induced intracellular calcium elevation, and exhibits the characteristic of slow dissociation from striatal A2a receptors in primates. ASP5854 reverses catalepsy, enhances cognitive ability, improves motor function and exerts neuroprotective effects, while also alleviating dyskinesia and increasing contralateral turning behavior. ASP5854 is mainly used in studies related to ischemic stroke and Parkinson's disease.
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- CAS No.: 851087-60-0
- Formula: C18H17FN4O
- Molecular Weight:324.35
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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
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Biological Activity
Description
In Vitro
ASP5854 (various concentrations; 60 min) potently and selectively binds to human, rat, and mouse adenosine A1 and A2a receptors, with Ki values ranging from 1.24 to 12.48 nM, and exhibits no significant affinity for A3 receptors[2].
ASP5854 displays dual A2A/A1 AR binding affinity with a Ki of 1.76 nM at human A2A AR and 9.03 nM at human A1 AR[1].
ASP5854 (various concentrations; 10 s) acts as a potent functional antagonist of human adenosine A1 and A2a receptors in transfected CHO cells, inhibiting agonist-induced intracellular Ca2+ elevation with IC50 values of 59.81 nM and 4.21 nM, respectively[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
ASP5854 (0.01-3.2 mg/kg; p.o.; single dose) dose-dependently reverses haloperidol-induced catalepsy in mice with an ED50 of 0.066 mg/kg, showing significant efficacy at doses ≥0.1 mg/kg[2].
ASP5854 (0.01-1 mg/kg; p.o.; single dose) reduces haloperidol-induced cataleptic duration in rats, with significant efficacy starting at a dose of 0.1 mg/kg[2].
ASP5854 (0.01-1 mg/kg; p.o.; single dose) significantly potentiates L-DOPA-induced contralateral turning behavior in 6-hydroxydopamine-lesioned hemiparkinsonian rats at doses of 0.032 to 1 mg/kg[2].
ASP5854 (0.032-3.2 mg/kg; p.o.; single dose) reverses scopolamine-induced spontaneous alternation deficits in the mouse Y-maze test, showing significant efficacy at doses of 0.32 and 1 mg/kg[2].
ASP5854 (0.032-1 mg/kg; p.o.; single dose) reverses MK-801-induced spontaneous alternation deficits in the mouse Y-maze test, showing significant efficacy at doses of 0.32 and 1 mg/kg[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ddY mice (male, 7 weeks old, intracerebroventricular injection of CGS21680-induced catalepsy)[2]
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Dosage:0.01 mg/kg; 0.032 mg/kg; 0.1 mg/kg; 0.32 mg/kg; 1 mg/kg; 3.2 mg/kg
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Administration:p.o.; single dose
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Result:Dose-dependently ameliorated CGS21680-induced catalepsy, with an ED50 value of 0.147 mg/kg.
Showed statistically significant effects at doses of 0.32 mg/kg and higher.
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Animal Model:Sprague-Dawley rats (male, 7 weeks old, intraperitoneal injection of haloperidol-induced catalepsy)[2]
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Dosage:0.01 mg/kg; 0.032 mg/kg; 0.1 mg/kg; 0.32 mg/kg; 1 mg/kg
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Administration:p.o.; single dose
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Result:Reduced the cataleptic duration, with a minimum effective dose of 0.1 mg/kg.
Showed statistically significant reductions at doses of 0.1 mg/kg and higher.
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Animal Model:Fisher rats (male, 14 weeks old at surgery, stereotaxic unilateral injection of 6-hydroxydopamine-induced hemiparkinsonism, selected based on apomorphine-induced contralateral rotations)[2]
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Dosage:0.01 mg/kg; 0.032 mg/kg; 0.1 mg/kg; 0.32 mg/kg; 1 mg/kg
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Administration:p.o.; single dose
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Result:Significantly potentiated L-DOPA-induced contralateral turning behavior at doses of 0.032 to 1 mg/kg.
Minimally induced turning behavior when administered alone.
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Animal Model:Wistar rats (male, 8 weeks old, intraperitoneal injection of scopolamine-induced memory deficits in passive avoidance test)[2]
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Dosage:0.032 mg/kg; 0.1 mg/kg; 0.32 mg/kg; 1 mg/kg; 3.2 mg/kg
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Administration:i.p.; single dose
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Result:Prolonged retention latency in scopolamine-treated rats in a bell-shaped dose-response manner.
Showed statistically significant effects at doses of 0.1 to 3.2 mg/kg.
Chemical Information
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CAS No. 851087-60-0
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Molecular Weight 324.35
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Formula C18H17FN4O
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SMILES
O=C1C=CC(C2=NC=C(N)N=C2C3=CC=C(F)C=C3)=CN1C(C)C
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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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Human pluripotent stem cell midbrain dopaminergic neuron differentiation
Human pluripotent stem cells are directed toward midbrain dopaminergic neurons by first inducing a neural floor-plate-like progenitor state, then patterning cells with ventralizing SHH signaling and midbrain/WNT-FGF cues, and finally maturing progenitors into neurons expressing dopaminergic markers such as TH, NURR1/NR4A2, PITX3, DAT/SLC6A3, VMAT2/SLC18A2, GIRK2/KCNJ6, FOXA2, LMX1A, and EN1. The main readouts are loss of pluripotency, acquisition of FOXA2+/LMX1A+ midbrain floor-plate progenitors, emergence of βIII-tubulin+/MAP2+ neurons, and production of TH+ dopaminergic neurons with molecular, dopamine-release, and electrophysiological features of midbrain dopaminergic identity.
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Calcium Spark Assay
Calcium sparks are localized, transient increases in intracellular calcium concentration ([Ca2+]i) that occur in cardiac myocytes and represent elementary events underlying excitation-contraction coupling. These events are generated by the coordinated opening of clusters of ryanodine receptors (RyRs) on the sarcoplasmic reticulum membrane, leading to a brief release of Ca2+ into the cytosol. The detection and analysis of calcium sparks provide insights into the mechanisms of calcium handling and signaling in cardiac cells. Imaging techniques using fluorescent calcium indicators such as Fluo-3 are employed to visualize these subcellular calcium transients with high spatial and temporal resolution. The protocol is based on established methodologies described in primary literature for both experimental measurement and automated analysis of calcium sparks.
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Ca2+ Staining Technique
Ca2+ staining is an experimental technique that utilizes specific fluorescent probes (such as Fluo-4 AM, Fura-2, etc.) to qualitatively or quantitatively detect dynamic changes in intracellular Ca2+ concentrations; this is achieved by monitoring the changes in fluorescent signals generated when these probes bind to free intracellular calcium ions. The underlying principle relies primarily on the presence of chelating groups within the probe's molecular structure that possess high affinity for calcium ions.
Purity & Documentation
References
[1]. Tang ML, et al. Discovery of Pyridone-Substituted Triazolopyrimidine Dual A2A/A1 AR Antagonists for the Treatment of Ischemic Stroke. ACS Med Chem Lett. 2022;13(3):436-442. Published 2022 Feb 21. [Content Brief]
[3]. Brunschweiger A, et al. 8-Benzyltetrahydropyrazino[2,1-f]purinediones: water-soluble tricyclic xanthine derivatives as multitarget drugs for neurodegenerative diseases. ChemMedChem. 2014;9(8):1704-1724. [Content Brief]
[4]. Mihara T, et al. Brain adenosine A2A receptor occupancy by a novel A1/A2A receptor antagonist, ASP5854, in rhesus monkeys: relationship to anticataleptic effect. J Nucl Med. 2008;49(7):1183-1188. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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