Physicochemical Properties
| Molecular Formula | C₂₁H₁₅F₂N₅O |
| Molecular Weight | 391.37 |
| Exact Mass | 391.124 |
| CAS # | 425377-76-0 |
| PubChem CID | 9865233 |
| Appearance | Light yellow to green yellow solid powder |
| Density | 1.4±0.1 g/cm3 |
| Index of Refraction | 1.658 |
| LogP | 1.36 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 29 |
| Complexity | 640 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | PCZLQMGFNUNVOM-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H15F2N5O/c1-21(2,29)18-11-26-28-17(10-25-20(28)27-18)12-6-7-15(22)14(8-12)19-13(9-24)4-3-5-16(19)23/h3-8,10-11,29H,1-2H3 |
| Chemical Name | 3-fluoro-2-[2-fluoro-5-[3-(2-hydroxypropan-2-yl)imidazo[1,2-b][1,2,4]triazin-7-yl]phenyl]benzonitrile |
| Synonyms | TPA023B; TPA 023B |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | TPA-023B exhibits a high affinity for the human recombinant GABAA receptor's α5 isoform (Ki 1.1 nM), whereas its affinity for the isoforms that contain α4 and α6 is more than 1500 times lower (Ki > 1000 nM). Additionally, TPA-023B exhibits a high degree of affinity for native rat GABAA receptors in the frontal cortex, spinal cord, and cerebellum (Ki 0.32-0.99 nM) [1]. In cells expressing α1 isoform, TPA-023B inhibits chlordiazepoxide's capacity to increase GABA EC20-induced currents. To be more precise, 3 μM chlordiazepoxide increased GABA EC20 currents by 105%; however, this impact was only 8% when 100 nM TPA-023B was present [1]. |
| ln Vivo | Using an in vivo [3H]flumazenil binding assay, TPA-023B produced dosage- and time-dependent occupancy of rat brain GABAA receptors, with 50% occupancy matching to the relevant dose and plasma drug concentration of 0.09 mg/kg and 19 ng/ml[1]. The highest dose (10 mg/kg) of TPA-023B corresponds to an occupancy rate greater than 99% in rodents and primates (squirrel monkeys) with ataxia and/or muscle flaccidity, but not in rodents or in primates with conditioned drinking inhibition, fear-potentiated startle, elevated plus maze, or conditioned emotional responses [1]. |
| References |
[1]. Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist. J Psychopharmacol. 2011 Mar;25(3):329-44. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~255.51 mM) |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5551 mL | 12.7756 mL | 25.5513 mL | |
| 5 mM | 0.5110 mL | 2.5551 mL | 5.1103 mL | |
| 10 mM | 0.2555 mL | 1.2776 mL | 2.5551 mL |