| 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 |
| Targets |
Afizagabar selectively targets α5-subunit-containing GABAA receptors. It exhibits an IC50 of 585 nM for α5β2γ2 and a Ki of 66 nM for α5β3γ2. The compound acts as a competitive antagonist with a Kb of 221 nM. It selectively inhibits extrasynaptic α5-GABAARs in mouse CA1 pyramidal neurons.
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| ln Vitro |
S44819. Afizagabar is a competitive antagonist of α5-GABAAR (Kb=221 nM). Afizagabar inhibits mouse CA1 pyramidal neurons' extrasynaptic α5-GABAARs in a specific manner[1].
In cell-free receptor binding assays, Afizagabar demonstrates high-affinity binding to α5-GABAARs with a Ki of 66 nM. It competitively displaces GABA from the orthosteric binding site. The compound shows selectivity for α5-containing receptors over other GABAA receptor subtypes. In cellular electrophysiology studies, Afizagabar selectively inhibits extrasynaptic α5-GABAARs in mouse CA1 pyramidal neurons. The compound acts as a competitive antagonist at the GABA-binding site. Its antagonistic activity is concentration-dependent, with a Kb of 221 nM. The compound does not affect synaptic GABAA receptors, demonstrating functional selectivity. |
| ln Vivo |
Afizagabar (1 and 3 mg/kg; ip) considerably reduces the notable rise in overall mistakes brought on by Scopolamine[1].
In vivo studies on Afizagabar are limited, as the compound is primarily characterized in vitro. Its selective antagonism of α5-GABAARs suggests potential applications in cognitive enhancement, as α5-GABAARs are implicated in learning and memory. In vivo efficacy studies would be required to confirm these effects. |
| Enzyme Assay |
Cell-free receptor binding assays for Afizagabar are performed using membrane preparations from cells expressing recombinant α5-GABAARs. Radioligand displacement studies use [³H]muscimol or other GABAA receptor ligands. Membranes are incubated with varying concentrations of Afizagabar and the radioligand, followed by filtration and scintillation counting. Ki values are calculated from competition binding curves.
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| Cell Assay |
Cellular electrophysiology experiments are conducted using patch-clamp recordings from mouse CA1 pyramidal neurons or cells expressing recombinant α5-GABAARs. Afizagabar is applied at various concentrations, and GABA-induced currents are measured. The compound's antagonistic activity is assessed by its ability to reduce GABA-evoked responses. IC50 and Kb values are determined from concentration-response data.
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| Animal Protocol |
Animal/Disease Models: Male Sprague Dawley (SPRD) rats (In the eight-arm radial maze)[1]
Doses: 1 and 3 mg/kg Route of Administration: Ip Experimental Results: Dramatically diminished the marked increase in total errors induced by Scopolamine. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Afizagabar have not been extensively reported. As a small-molecule antagonist, it is expected to be capable of crossing the blood-brain barrier. Detailed PK parameters including oral bioavailability, half-life, and tissue distribution require further characterization.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for Afizagabar are limited. As a selective α5-GABAAR antagonist, it may have a favorable safety profile compared to non-selective GABAA receptor modulators. Comprehensive toxicological studies would be required for therapeutic development.
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| References | |
| Additional Infomation |
Afizagabar is a small molecule drug. It is currently undergoing clinical trial NCT02877615 (a trial of the efficacy and safety of S 44819 after recent ischemic stroke). The monoisotope molecular weight of afizagabar is 365.06 Da. It is a tricyclic oxazolo-2,3-benzodiazepine derivative.
Afizagabar is a first-in-class α5-GABAAR antagonist with potential applications in cognitive disorders. Its selectivity for α5-containing receptors distinguishes it from other GABAA receptor modulators. The compound is a valuable research tool for studying the role of α5-GABAARs in neurological function. It is not approved for clinical use. |
| Molecular Formula |
C19H12FN3O2S
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|---|---|
| Molecular Weight |
365.380886077881
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| Exact Mass |
365.063
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| Elemental Analysis |
C, 62.46; H, 3.31; F, 5.20; N, 11.50; O, 8.76; S, 8.77
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| CAS # |
1398496-82-6
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| PubChem CID |
136209703
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
26
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| Complexity |
669
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C2C=CC=C(C=2C=C1C1C2=CC3=C(C=C2CC(C)=NN=1)NC(=O)O3)F
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| InChi Key |
WNUWGRVHGICCLS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H12FN3O2S/c1-9-5-10-6-14-15(25-19(24)21-14)7-11(10)18(23-22-9)17-8-12-13(20)3-2-4-16(12)26-17/h2-4,6-8H,5H2,1H3,(H,21,24)
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| Chemical Name |
5-(4-fluoro-1-benzothiophen-2-yl)-8-methyl-1,9-dihydro-[1,3]oxazolo[4,5-h][2,3]benzodiazepin-2-one
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| Synonyms |
Afizagabar; S44819; S-44819; S 44819; Egis 13529; Egis-13529; Egis13529; 1398496-82-6; s44,819; ZD6M94A8IH; S-44,819;
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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: 6.25 mg/mL (17.11 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 | 2.7369 mL | 13.6844 mL | 27.3688 mL | |
| 5 mM | 0.5474 mL | 2.7369 mL | 5.4738 mL | |
| 10 mM | 0.2737 mL | 1.3684 mL | 2.7369 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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