| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
ONO-8590580 is a novel and potent GABAAα5 negative allosteric modulator which enhances long-term potentiation and improves cognitive deficits in preclinical models. ONO-8590580 binds to the benzodiazepine binding sites on recombinant human α5-containing GABAA receptors with a Ki of 7.9 nM, and showed functionally selective GABAAα5 NAM activity for GABA-induced Cl- channel activity with a maximum 44.4% inhibition and an EC50 of 1.1 nM. In rat hippocampal slices, tetanus-induced long-term potentiation of CA1 synapse response was significantly augmented in the presence of 300 nM ONO-8590580. Orally administered ONO-8590580 (1-20 mg/kg) dose-dependently occupied hippocampal GABAAα5 in a range of 40%-90% at 1 hour after intake. In the rat passive avoidance test, ONO-8590580 (3-20 mg/kg, by mouth) significantly prevented (+)-MK-801 hydrogen maleate (MK-801)-induced memory deficit. In addition, ONO-8590580 (20 mg/kg, p.o.) was also effective in improving the cognitive deficit induced by scopolamine and MK-801 in the rat eight-arm radial maze test with equal or greater activity than 0.5 mg/kg donepezil. No anxiogenic-like or proconvulsant effect was associated with ONO-8590580 at 20 mg/kg p.o. in the elevated plus maze test or pentylenetetrazole-induced seizure test, respectively. In sum, ONO-8590580 is a novel GABAAα5 NAM that enhances hippocampal memory function without an anxiogenic or proconvulsant risk.
| ln Vivo |
The effect of ONO-8590580 on MK-801/scopolamine-induced cognitive impairments in the 8-arm radial maze test was examined. The dosages of MK-801 and scopolamine in this trial were 0.075 mg/kg (ip) and 0.2 mg/kg (ip), respectively. ONO-8590580 (20 mg/kg, po) significantly reduced the number of mistakes and total delay compared to control. In the current study, ONO-8590580, but not donepezil, considerably reduced the number of errors, which may imply that ONO-8590580 may be more successful in the treatment of AD patients. The observations showing that ONO-8590580 does not have anxiogenic or proconvulsant effects are compatible with the behavioral phenotype of α5-/- mice [1].
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| References |
| Molecular Formula |
C21H21FN6
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|---|---|
| Molecular Weight |
376.430046796799
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| Exact Mass |
376.181
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| CAS # |
1802661-73-9
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| PubChem CID |
118278442
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| Appearance |
White to off-white solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
545
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C(C)=C2N=CN(C2=CC=1NC1C=CC(C2=CN(C)C=N2)=CN=1)CC1CC1
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| InChi Key |
INGJMHPGMVUEKY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H21FN6/c1-13-20(22)16(7-18-21(13)25-12-28(18)9-14-3-4-14)26-19-6-5-15(8-23-19)17-10-27(2)11-24-17/h5-8,10-12,14H,3-4,9H2,1-2H3,(H,23,26)
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| Chemical Name |
1-(Cyclopropylmethyl)-5-fluoro-4-methyl-N-(5-(1-methyl-1H-imidazol-4-yl)pyridin-2-yl)-1H-benzo[d]imidazol-6-amine
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| Synonyms |
ONO8590580; ONO 8590580; ONO-8590580
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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 : ~62.5 mg/mL (~166.03 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.53 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.53 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6565 mL | 13.2827 mL | 26.5654 mL | |
| 5 mM | 0.5313 mL | 2.6565 mL | 5.3131 mL | |
| 10 mM | 0.2657 mL | 1.3283 mL | 2.6565 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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