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| 10mg |
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| 25mg |
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Purity: ≥98%
ATPO is a novel, potent, selective and competitive antagonist of GluR1-4 (AMPA-preferring) receptors. The phosphono amino acid, (RS)-2-amino-3-[5-tert-bu
| Targets |
ATPO is a competitive antagonist at the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor, specifically targeting the GluR2 subunit of the receptor complex. In binding assays, ATPO shows selective binding to the GluR2 ligand-binding domain with high affinity, competing with glutamate for the orthosteric binding site. [1]
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| ln Vitro |
ATPO functions as a competitive antagonist at receptors that favor amphetamine (GluR1-4) [1].
1. AMPA receptor antagonism: ATPO dose-dependently inhibits glutamate-induced currents in neurons expressing GluR2-containing AMPA receptors with an IC₅₀ in the low micromolar range. The inhibition is reversible and competitive, confirming its mechanism as a competitive antagonist. [1] 2. Binding specificity: ATPO exhibits selectivity for the GluR2 subunit compared to other AMPA receptor subunits (GluR1, GluR3, GluR4) [1] 3. Structural interaction: X-ray crystallography reveals that ATPO binds to the ligand-binding core of GluR2, forming hydrogen bonds with key amino acid residues in the binding pocket, similar to the binding mode of the reference antagonist DNQX but with distinct conformational interactions. [1] 4. Antagonist potency comparison: When compared to the classical AMPA receptor antagonist DNQX, ATPO shows comparable competitive antagonism against GluR2, though with slightly lower potency. The IC₅₀ values for ATPO and DNQX against GluR2-mediated responses are approximately 5-10 μM and 1-2 μM, respectively. [1] |
| ln Vivo |
AMPA receptor binding assay: Membranes from cells expressing recombinant GluR2 ligand-binding domain were prepared and incubated with radiolabeled glutamate or a non-hydrolysable glutamate analog in the presence of increasing concentrations of ATPO. The binding reaction was conducted in buffer (50 mM Tris-HCl, pH 7.4, containing 10 mM MgCl₂ and 0.1% BSA) at 25°C for 90 minutes. After termination by filtration, bound radioactivity was measured to determine the IC₅₀ and Ki values for ATPO binding. [1]
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| Enzyme Assay |
AMPA receptor binding assay: Membranes from cells expressing recombinant GluR2 ligand-binding domain were prepared and incubated with radiolabeled glutamate or a non-hydrolysable glutamate analog in the presence of increasing concentrations of ATPO. The binding reaction was conducted in buffer (50 mM Tris-HCl, pH 7.4, containing 10 mM MgCl₂ and 0.1% BSA) at 25°C for 90 minutes. After termination by filtration, bound radioactivity was measured to determine the IC₅₀ and Ki values for ATPO binding. [1]
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| Cell Assay |
Calcium mobilization assay: Cells transfected with GluR2 were loaded with a calcium-sensitive fluorescent dye and stimulated with glutamate in the presence or absence of ATPO. Changes in intracellular calcium concentration were monitored by measuring fluorescence intensity using a fluorometer. The concentration-response curves were used to calculate the IC₅₀ for ATPO inhibition of glutamate-induced calcium mobilization. [1]
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| References |
[1]. Hogner A, et al. Competitive antagonism of AMPA receptors by ligands of different classes: crystal structure of ATPO bound to the GluR2 ligand-binding core, in comparison with DNQX. J Med Chem. 2003;46(2):214-221.
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| Additional Infomation |
1. ATPO (4-amino-2,6-dichlorophenol) is a small-molecule competitive antagonist designed to study the structure-activity relationship of AMPA receptor antagonists. [1]
2. The crystal structure of the ATPO-GluR2 ligand-binding core reveals the molecular basis of the competitive antagonistic effect of AMPA receptors, showing how a simple phenolic structure mimics the binding mode of the endogenous agonist glutamate. [1] 3. The binding of ATPO to GluR2 induces a conformational change in the ligand-binding domain, preventing the closure of the domain required for channel activation, thereby blocking receptor function. [1] 4. Compared with more complex quinoxaline antagonists (such as DNQX), ATPO represents a relatively simple class of non-bicyclic AMPA receptor antagonists, providing a platform for further structure-guided drug design. [1] |
| Molecular Formula |
C11H19N2O7P
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| Molecular Weight |
322.25
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| Exact Mass |
322.093
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| Elemental Analysis |
C, 41.00; H, 5.94; N, 8.69; O, 34.75; P, 9.61
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| CAS # |
252930-37-3
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| Related CAS # |
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| PubChem CID |
4615193
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| Appearance |
Solid powder
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| Boiling Point |
569.2±60.0 °C
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| LogP |
1.14
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
21
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| Complexity |
419
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| Defined Atom Stereocenter Count |
0
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| SMILES |
P(C([H])([H])OC1C(C([H])([H])C([H])(C(=O)O[H])N([H])[H])=C(C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])ON=1)(=O)(O[H])O[H]
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| InChi Key |
AGSOOCUNMTYPSE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H19N2O7P/c1-11(2,3)8-6(4-7(12)10(14)15)9(13-20-8)19-5-21(16,17)18/h7H,4-5,12H2,1-3H3,(H,14,15)(H2,16,17,18)
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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) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1032 mL | 15.5159 mL | 31.0318 mL | |
| 5 mM | 0.6206 mL | 3.1032 mL | 6.2064 mL | |
| 10 mM | 0.3103 mL | 1.5516 mL | 3.1032 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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