| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
RO4938581 targets the GABAA receptor, specifically the α5 subunit-containing receptor. It acts as a potent and selective inverse agonist at the GABAA α5β3γ2a receptor with a Ki of 4.6 nM. It shows lower affinity at α1β3γ2a (Ki = 174 nM), α2β3γ2a (Ki = 185 nM), and α3β3γ2a (Ki = 80 nM).
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| ln Vitro |
RO 4938581 is a strong and specific inverse agonist for GABAA α5; its Ki for GABAA α5β3η2a is 4.6 nM, whereas its affinity for α1β3η2a, α2β3η2a, and α3β3η2a is 174, 185, and 80 nM, respectively [1].
In vitro, RO4938581 is a potent and selective GABAA α5 inverse agonist with a Ki of 4.6 nM for GABAA α5β3γ2a. It shows significantly lower affinity at other GABAA receptor subtypes (α1, α2, α3). This selectivity for the α5 subunit makes RO4938581 a valuable tool for studying the role of α5-containing GABAA receptors in cognitive function. |
| ln Vivo |
RO 4938581 (0.3-1 mg/kg, p.o.) reverses the delayed matching place (DMTP) task's effects on working memory, scopolamine's effects on working memory, and diazepam's (RO 4938581; 1–10 mg/kg, PO) effects on spatial learning [1].
In vivo, RO4938581 (0.3-1 mg/kg, p.o.) reverses a working memory impairment induced by scopolamine in the delayed match to position (DMTP) task. RO4938581 (1-10 mg/kg, p.o.) reverses a spatial learning impairment induced by diazepam. These findings demonstrate the in vivo efficacy of RO4938581 in reversing cognitive deficits. |
| Enzyme Assay |
The GABAA receptor binding assay for RO4938581 involves incubating the compound with membrane preparations from cells expressing recombinant GABAA receptor subtypes (α1, α2, α3, α5 with β3 and γ2a) and a radiolabeled GABAA receptor ligand. After incubation, bound and free ligands are separated by filtration, and the radioactivity is counted. The Ki for displacement of the radioligand is calculated from the competition curve.
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| Cell Assay |
To evaluate the cellular activity of RO4938581, cells expressing GABAA receptors (such as oocytes or HEK293 cells transfected with GABAA receptor subunits) are used in electrophysiological studies. The compound's effect on GABA-induced chloride currents is measured using patch-clamp or two-electrode voltage-clamp techniques. The inverse agonist activity is assessed by the reduction of GABA-induced currents.
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| Animal Protocol |
The in vivo efficacy of RO4938581 is evaluated in rodent models of cognitive dysfunction. The delayed match to position (DMTP) task is used to assess working memory in rats. Scopolamine is administered to induce working memory impairment, and RO4938581 is given orally to assess its ability to reverse the deficit. Spatial learning is assessed using the Morris water maze or other spatial learning tasks, with diazepam used to induce learning impairment.
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| ADME/Pharmacokinetics |
RO4938581 has a molecular weight of 352.14 and a molecular formula of C13H8BrF2N5. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound is soluble in DMSO. It displays strong CYP1A2 autoinduction properties in rats. It is typically stored as a powder at -20°C.
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| Toxicity/Toxicokinetics |
Specific toxicity data for RO4938581 are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is a potent and selective GABAA α5 inverse agonist, and its toxicity profile would be expected to reflect its mechanism of action. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
RO4938581 is a potent and selective GABAA α5 inverse agonist with a Ki of 4.6 nM for GABAA α5β3γ2a. It shows lower affinity at α1β3γ2a, α2β3γ2a, α3β3γ2a (Ki values of 174 nM, 185 nM, and 80 nM, respectively). It reverses working memory and spatial learning impairments in rodent models. It is used in the research of cognitive dysfunction.
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| Molecular Formula |
C13H8BRF2N5
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|---|---|
| Molecular Weight |
352.136927604675
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| Exact Mass |
350.993
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| CAS # |
883093-10-5
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| PubChem CID |
11624499
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| Appearance |
White to off-white solid powder
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| Density |
1.9±0.1 g/cm3
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| Boiling Point |
559.8±60.0 °C at 760 mmHg
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| Flash Point |
292.4±32.9 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.784
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| LogP |
2.83
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
21
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| Complexity |
401
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
AFJRYPJIKHMNGL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H8BrF2N5/c14-7-1-2-9-8(3-7)13-17-5-19-21(13)4-10-11(12(15)16)18-6-20(9)10/h1-3,5-6,12H,4H2
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| Chemical Name |
15-bromo-5-(difluoromethyl)-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene
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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 (~283.98 mM)
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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 | 2.8398 mL | 14.1989 mL | 28.3978 mL | |
| 5 mM | 0.5680 mL | 2.8398 mL | 5.6796 mL | |
| 10 mM | 0.2840 mL | 1.4199 mL | 2.8398 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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