| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
IC50: 9.74 μM (TREK-1/TREK-1), 16.5 μM (TWIK-1/TREK-1)[1]
The primary target of TWIK-1/TREK-1-IN-3 is the TREK-1 potassium channel, a member of the two-pore domain potassium (K2P) channel family that plays a crucial role in maintaining resting membrane potential and regulating neuronal excitability. TREK-1 is an important target for antidepressant drug discovery. TWIK-1/TREK-1-IN-3 inhibits TREK-1 homodimers and TWIK-1/TREK-1 heterodimers, which are formed by the association of TREK-1 with TWIK-1. By blocking these channels, the compound modulates potassium ion flow, influencing processes such as pain perception, mood regulation, and neuroprotection. |
|---|---|
| ln Vitro |
In vitro, TWIK-1/TREK-1-IN-3 is a potent inhibitor of TREK-1 channels, with activity against both TREK-1 homodimers and TWIK-1/TREK-1 heterodimers. The compound is typically used in electrophysiological studies to examine channel function and is a valuable tool for studying the role of TREK-1 in neuronal excitability and mood regulation. It exhibits antidepressant activity in preclinical models. TWIK-1/TREK-1-IN-3 is soluble in DMSO at 20 mg/mL (53.7 mM) with sonication and is stored as a powder at -20°C for up to 3 years.
|
| ln Vivo |
In vivo, TWIK-1/TREK-1-IN-3 has potential applications in the study of depression due to its ability to inhibit TREK-1 channels. By modulating potassium ion flow and neuronal excitability, the compound may influence mood regulation and other neurological processes. However, detailed in vivo efficacy and safety data are not extensively reported in the available literature, and its use is primarily limited to preclinical research settings. Further studies are needed to fully characterize its in vivo effects and therapeutic potential.
|
| Enzyme Assay |
In vitro assays for TWIK-1/TREK-1-IN-3 typically involve measuring its inhibition of TREK-1 channel activity using electrophysiological techniques such as patch-clamp recording in cell lines expressing recombinant TREK-1 channels. The compound is applied to the cells at varying concentrations (typically in the micromolar range), and the resulting inhibition of potassium current is measured. The IC50 value is determined by fitting concentration-response curves. The compound's selectivity for TREK-1 over other K2P channels can be assessed by testing it on cells expressing other channel subtypes.
|
| Cell Assay |
Cellular assays for TWIK-1/TREK-1-IN-3 typically use cell lines expressing recombinant TREK-1 channels, such as CHO or HEK293 cells. The compound is applied to the cells, and its effects on channel activity are assessed using electrophysiological techniques such as patch-clamp recording. Fluorescent-based membrane potential assays using voltage-sensitive dyes can also be used for higher-throughput screening of channel activity. Cells are treated with TWIK-1/TREK-1-IN-3 at various concentrations (e.g., 0.1-100 µM), and the changes in membrane potential are measured. The IC50 for channel inhibition is determined from the concentration-response data.
|
| Animal Protocol |
In vivo animal studies for TWIK-1/TREK-1-IN-3 would likely involve the administration of the compound to rodent models of depression or other neurological disorders. The compound could be administered via intraperitoneal injection or oral gavage, depending on its bioavailability. Endpoints would include behavioral tests for antidepressant-like activity (such as the forced swim test or tail suspension test), as well as measurements of neuronal excitability and neurotransmitter levels. However, specific in vivo study protocols for TWIK-1/TREK-1-IN-3 are not detailed in the available literature.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for TWIK-1/TREK-1-IN-3 are not extensively reported in the available literature. The compound has a molecular weight of 372.43 g/mol and is soluble in DMSO at 20 mg/mL. It is a white solid with a purity of 99.04%. For research purposes, the compound is typically stored as a powder at -20°C for up to 3 years or in solution at -80°C for up to 1 year. Detailed parameters such as half-life, volume of distribution, and bioavailability are not publicly available and would need to be determined experimentally.
|
| Toxicity/Toxicokinetics |
There is no specific toxicity data reported for TWIK-1/TREK-1-IN-3 in the available literature. As a research chemical intended for laboratory use only, it should be handled with standard safety precautions for handling chemical reagents. The compound is not approved for human therapeutic use. Researchers should consult the material safety data sheet (MSDS) for detailed safety and handling information. Any potential toxicity would need to be assessed through formal toxicological studies if the compound were to be developed further.
|
| References |
[1]. Lee EH, et al. Novel potent blockers for TWIK-1/TREK-1 heterodimers as potential antidepressants. Biomed Pharmacother. 2023 Sep;165:115139.. .
|
| Additional Infomation |
TWIK-1/TREK-1-IN-3 (compound 2h) is a selective and potent inhibitor of the TREK-1 potassium channel. It has a molecular formula of C19H27F3N2O2 and a molecular weight of 372.43 g/mol. The compound inhibits TREK-1 homodimers and TWIK-1/TREK-1 heterodimers and exhibits antidepressant activity. It is used in the study of depression and is available with a purity of 99.04%. TWIK-1/TREK-1-IN-3 is soluble in DMSO and is stored at -20°C.
|
| Exact Mass |
372.202
|
|---|---|
| CAS # |
1440532-33-1
|
| PubChem CID |
118131592
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
26
|
| Complexity |
413
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C1CCN(C1)C2CCN(CC2)C[C@@H](COC3=CC=C(C=C3)C(F)(F)F)O
|
| InChi Key |
CGWZNOCWGMKTOS-KRWDZBQOSA-N
|
| InChi Code |
InChI=1S/C19H27F3N2O2/c20-19(21,22)15-3-5-18(6-4-15)26-14-17(25)13-23-11-7-16(8-12-23)24-9-1-2-10-24/h3-6,16-17,25H,1-2,7-14H2/t17-/m0/s1
|
| Chemical Name |
(2S)-1-(4-pyrrolidin-1-ylpiperidin-1-yl)-3-[4-(trifluoromethyl)phenoxy]propan-2-ol
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 25 mg/mL (67.13 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
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.) |
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
