| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
AS057278 targets D-amino acid oxidase (DAAO), a flavoenzyme that catalyzes the oxidative deamination of D-amino acids, particularly D-serine. D-serine is a co-agonist at the NMDA receptor, and its levels are regulated by DAAO. By inhibiting DAAO, AS057278 increases D-serine levels in the brain, enhancing NMDA receptor function. NMDA receptor hypofunction is implicated in the pathophysiology of schizophrenia. The compound is selective for DAAO and penetrates the blood-brain barrier. It normalizes PCP-induced prepulse inhibition deficits in mice.
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| ln Vitro |
In vitro, AS057278 is a potent and selective inhibitor of D-amino acid oxidase (DAAO). It inhibits the enzymatic activity of DAAO, preventing the degradation of D-serine. The compound is BBB penetrant and orally active. Detailed IC50 values for DAAO inhibition are not extensively reported in the available literature. The compound is used as a research tool for studying the role of DAAO and NMDA receptor function in schizophrenia.
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| ln Vivo |
AS057278 (PO; 20 mg/kg bid for 28 days; 80 mg/kg single dose) restores prepulse depression caused by phencyclidine (PCP) to normal [1]. The pharmacokinetic effects of AS057278 (10 mg/kg; oral and intravenous; single dose) are good [1]. AS057278's pharmacokinetic characteristics in male Sprague-Dawley rats [1]. IV (10 mg/kg) PO (10 mg/kg) C0 (ng/mL) 100,557.3 Cmax (ng/mL) 73,559.8 8088.8 tmax (h) 0.083 1 CZ (ng/mL) 26.8 40.5 tZ (h) 24 24 AUCZ (ng/mL·h) 45,596.2 18,254.4 λZ (h^-1) 0.124 0.096 AUC (ng/mL·h) 45,810.9 18,649.9 VZ (L/kg) 1.76 VSS (L/kg) 0.24 CL (L/kg/h) 0.22 MRT (h) 1.087 F 0.407
In vivo, AS057278 normalizes phencyclidine (PCP)-induced prepulse inhibition deficits in mice after both acute (80 mg/kg) and chronic (20 mg/kg b.i.d.) oral administration. It also shows efficacy after chronic oral treatment at 10 mg/kg. The compound's ability to reverse PCP-induced deficits in prepulse inhibition, a measure of sensorimotor gating, supports its potential as a therapeutic agent for schizophrenia. It is orally active and penetrates the blood-brain barrier. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for AS057278 typically involve DAAO activity assays using purified recombinant DAAO enzyme. The assay is performed in 96-well plates with assay buffer (50 mM Tris-HCl pH 8.0, 0.1 mg/mL horseradish peroxidase, 0.05 mM o-dianisidine). The compound (typically 0.001-100 μM) is incubated with the enzyme and D-serine substrate at 37°C for 30 minutes. The reaction product, H2O2, is detected by colorimetric measurement at 450 nm. The IC50 is determined from dose-response curves.
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| Cell Assay |
In vitro cellular assays for AS057278 use neuronal cell lines or primary neurons to assess effects on NMDA receptor function and D-serine levels. Cells are cultured in appropriate media and treated with various concentrations of the compound (typically 0.01-100 μM) for 4-24 hours. D-serine levels in culture supernatant are measured by HPLC or ELISA. NMDA receptor activity can be assessed by calcium imaging or electrophysiology. Cell viability is assessed using MTT assays.
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| Animal Protocol |
Animal/Disease Models: Male C57BL/6J mouse[1]
Doses: 80 mg/kg, 20 mg/kg Route of Administration: oral; 20 mg/kg bid, 28 days; 80 mg/kg Single dose Experimental Results: Standardized phencyclidine (PCP)-induced prepulse depression after acute (80 mg/kg) and chronic (20 mg/kg bid) oral administration in mice. Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat [1] Doses: 10 mg/kg Route of Administration: oral and intravenous (iv) (iv)injection; single dose (pharmacokinetic/PK/PK analysis) Experimental Results: demonstrated good pharmacokinetic/PK/PK effect. In vivo animal studies with AS057278 use mouse models of schizophrenia, particularly the phencyclidine (PCP)-induced prepulse inhibition (PPI) deficit model. Mice are administered PCP (5 mg/kg, s.c.) and treated with the compound orally at doses of 10-80 mg/kg. Prepulse inhibition of the acoustic startle response is measured using startle chambers. Locomotor activity is also assessed. D-serine levels in brain tissue and cerebrospinal fluid can be measured. Other behavioral tests (e.g., social interaction, novel object recognition) may be performed. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of AS057278: The compound is orally active and penetrates the blood-brain barrier. It has a molecular weight of 126.11 and is soluble in DMSO (25 mg/mL). Specific PK parameters such as Cmax, Tmax, AUC, half-life, and tissue distribution are not extensively reported in the available literature. As a small molecule, it is expected to have good oral bioavailability and brain penetration.
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| Toxicity/Toxicokinetics |
The toxicity profile of AS057278 is not extensively reported in the available literature. The compound is for research use only and not for human therapeutic use. Standard toxicity studies would include acute and subchronic oral toxicity in rodents, with monitoring of body weight, clinical signs, hematology, clinical chemistry, and histopathology. No specific genotoxicity or cardiotoxicity data are reported.
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| References |
[1]. Adage T, et al. In vitro and in vivo pharmacological profile of AS057278, a selective d-amino acid oxidase inhibitor with potential anti-psychotic properties. Eur Neuropsychopharmacol. 2008;18(3):200-214.
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| Additional Infomation |
5-Methylpyrazole-3-carboxylic acid is a type of pyrazole compound, consisting of a methyl group at the 5-position and a carboxylic acid group at the 3-position of 1H-pyrazole. It is a metabolite. It belongs to the pyrazole class and is a monocarboxylic acid. It is derived from the hydride of 1H-pyrazole.
AS057278 (CAS 402-61-9) is a potent, selective, orally active, and BBB-penetrant inhibitor of D-amino acid oxidase (DAAO) used to study schizophrenia. It normalizes phencyclidine (PCP)-induced prepulse inhibition deficits in mice after acute and chronic oral administration. By inhibiting DAAO, it increases D-serine levels and enhances NMDA receptor function. The compound is available for research purposes only and is not approved for clinical use. |
| Molecular Formula |
C5H6N2O2
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|---|---|
| Molecular Weight |
126.11334
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| Exact Mass |
126.043
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| CAS # |
402-61-9
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| PubChem CID |
9822
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.404g/cm3
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| Boiling Point |
388.8ºC at 760mmHg
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| Melting Point |
241 °C
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| Flash Point |
188.9ºC
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| Index of Refraction |
1.595
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| LogP |
0.416
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
9
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| Complexity |
126
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=C(C)[NH]N=C1C(O)=O
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| InChi Key |
WSMQKESQZFQMFW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C5H6N2O2/c1-3-2-4(5(8)9)7-6-3/h2H,1H3,(H,6,7)(H,8,9)
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| Chemical Name |
5-methyl-1H-pyrazole-3-carboxylic acid
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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 |
| 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) |
DMSO : ≥ 100 mg/mL (~792.96 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (19.82 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 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (19.82 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (19.82 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 | 7.9296 mL | 39.6479 mL | 79.2959 mL | |
| 5 mM | 1.5859 mL | 7.9296 mL | 15.8592 mL | |
| 10 mM | 0.7930 mL | 3.9648 mL | 7.9296 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.
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