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| Other Sizes |
| Targets |
GI-530159 targets the mechanosensitive two-pore-domain potassium (K2P) channels TREK1 (K2P2.1) and TREK2 (K2P10.1). It functions as a selective opener of these channels. These channels are important regulators of neuronal excitability and are involved in pain perception. The compound shows remarkable selectivity for TREK1/2 over other K2P channels like TRAAK and TASK3.
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| ln Vitro |
Pain perception is mediated by TREK (TWIK related K) two pore domain potassium (K2P) channels, which also modify the excitability of somatosensory nociceptive neurons [1]. TREK1 and TREK2 channels were selectively activated by GI-530159 (1 µM or 10 µM), while TRAAK and K channels were not significantly affected [1]. Recombinant human TREK1 channels are activated by GI-530159 (0.1-30 µM), with EC50s of 0.8 µM and 0.9 µM, respectively, based on Rb efflux and electrophysiology experiments [1]. Rat dorsal root ganglion (DRG) neurons' excitability is decreased by GI-530159 (1 µM), which causes a small hyperpolarization of the RMP and a decrease in firing frequency [1].
In vitro, GI-530159 demonstrates potent and selective activation of TREK1 and TREK2 channels. It activates recombinant human TREK1 channels with EC50 values of 0.8 μM (in Rb+ efflux assays) and 0.9 μM (in electrophysiology experiments). At a concentration of 1 μM, it significantly reduces the excitability of cultured rat DRG neurons, leading to a decreased firing frequency and a small hyperpolarization of the resting membrane potential. |
| ln Vivo |
In vivo, GI-530159 reduces the excitability of rat dorsal root ganglion neurons, which underpins its potential analgesic effect. As a selective opener of TREK1/2 channels, it is expected to modulate pain perception in animal models. While direct in vivo efficacy data is limited in the search results, its mechanism of action points to a potential for treating pain.
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| Enzyme Assay |
In vitro receptor binding and functional assays for GI-530159 typically involve measuring its ability to activate TREK1 and TREK2 channels. This can be assessed using Rb+ efflux assays or electrophysiological patch-clamp techniques on cells expressing the recombinant channels. The compound's selectivity is determined by testing its activity against a panel of other potassium channels, such as TRAAK and TASK3.
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| Cell Assay |
In vitro cell-based assays for GI-530159 involve evaluating its effects on neuronal excitability. Primary cultures of rat dorsal root ganglion (DRG) neurons are treated with the compound, and its impact on neuronal activity is measured using electrophysiological recordings. Parameters such as firing frequency and resting membrane potential are assessed to quantify the compound's inhibitory effect.
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| Animal Protocol |
In vivo animal experiments for GI-530159 have focused on its effects on pain perception. While detailed protocols are not specified in the search results, its mechanism as a TREK1/2 opener suggests it would be evaluated in standard pain models, such as the formalin test or von Frey test, to assess its analgesic potential.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for GI-530159 is not extensively detailed in the search results. The compound is a small molecule with a molecular weight of 518.45. It is typically dissolved in DMSO for in vitro studies. For in vivo studies, standard formulations using solvents like DMSO, PEG300, Tween 80, and saline can be used.
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| Toxicity/Toxicokinetics |
Available toxicity data for GI-530159 indicates it is harmful if swallowed (H302), causes skin irritation (H315), and causes serious eye irritation (H319). Standard safety precautions, including wearing protective gloves and eye protection, should be taken when handling the compound.
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| References | |
| Additional Infomation |
GI-530159 is a novel, selective opener of the TREK1 and TREK2 potassium channels, with potential applications in pain research. It reduces the excitability of sensory neurons, which are key mediators of pain perception. As a research compound, it is a valuable tool for studying the role of K2P channels in nociception and neuronal excitability. It is also known as ICA-069771.
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| Molecular Formula |
C27H20F6N2O2
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| Molecular Weight |
518.4503
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| Exact Mass |
518.142
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| CAS # |
69563-88-8
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| PubChem CID |
94652
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
544.8±50.0 °C at 760 mmHg
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| Melting Point |
159-163 °C(lit.)
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| Flash Point |
283.3±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.579
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| LogP |
4.57
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
37
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| Complexity |
641
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
HHLMWQDRYZAENA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H20F6N2O2/c28-26(29,30)25(27(31,32)33,17-1-9-21(10-2-17)36-23-13-5-19(34)6-14-23)18-3-11-22(12-4-18)37-24-15-7-20(35)8-16-24/h1-16H,34-35H2
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| Chemical Name |
4-[4-[2-[4-(4-aminophenoxy)phenyl]-1,1,1,3,3,3-hexafluoropropan-2-yl]phenoxy]aniline
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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 : ~250 mg/mL (~482.21 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 | 1.9288 mL | 9.6441 mL | 19.2883 mL | |
| 5 mM | 0.3858 mL | 1.9288 mL | 3.8577 mL | |
| 10 mM | 0.1929 mL | 0.9644 mL | 1.9288 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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