| Size | Price | Stock | Qty |
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| 25mg |
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| Targets |
ICI-204448 targets the κ-opioid receptor (KOR) as a peripherally acting agonist. Its peripheral activity is a key feature, as it acts on peripheral KOR rather than central nervous system receptors. This peripheral restriction allows the compound to produce analgesic and other effects without causing central side effects typically associated with KOR activation, such as sedation or dysphoria. The compound's mechanism involves activation of peripheral KOR, which modulates pain signaling and thermoregulation.
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| ln Vitro |
In vitro studies demonstrate that ICI-204448 hydrochloride is a peripherally acting KOR agonist. It binds to KOR with high affinity and selectivity. The compound's peripheral restriction is a key feature that distinguishes it from centrally acting KOR agonists. In vitro characterization includes receptor binding assays to determine affinity and selectivity for KOR over other opioid receptors. The compound's ability to activate KOR without crossing the blood-brain barrier has been demonstrated in cell-based and membrane-based assays. It is a valuable tool for studying peripheral KOR pharmacology.
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| ln Vivo |
In vivo studies of ICI-204448 hydrochloride have demonstrated its effects on thermoregulation and pain. In rats exposed to cold environments, ICI-204448 induced hypothermia, highlighting its impact on thermoregulation through peripheral KOR activation. The compound has also been studied for its analgesic effects in various pain models. Its peripheral activity allows it to produce effects without central side effects such as sedation or dysphoria. Studies have also explored its potential in identifying novel KOR-selective ligands with functional selectivity. Further research is ongoing to characterize its full in vivo profile.
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| Enzyme Assay |
For KOR binding assays, membrane preparations from cells expressing recombinant KOR or from peripheral tissues are incubated with radiolabeled ligands (e.g., [3H]-U69,593) and varying concentrations of ICI-204448 hydrochloride. Non-specific binding is determined using excess unlabeled reference compounds (e.g., nor-binaltorphimine). Following incubation at appropriate temperature (typically 25°C for 60-90 minutes), bound and free radioligands are separated by rapid filtration through glass fiber filters. Filters are washed and radioactivity counted by liquid scintillation. Ki values are calculated from competition curves using the Cheng-Prusoff equation. Assays are performed in triplicate with appropriate vehicle controls.
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| Cell Assay |
For in vitro cellular assays, cell lines expressing KOR (e.g., CHO or HEK293 cells) or primary peripheral neurons are cultured in appropriate media under standard conditions (37°C, 5% CO2). ICI-204448 hydrochloride is dissolved in DMSO and diluted in culture medium to desired concentrations. Cells are treated with compound for specified durations. KOR activation is assessed by measuring downstream signaling (e.g., G protein activation, cAMP inhibition, or calcium flux). Cell viability and cytotoxicity can be assessed using standard assays. Each concentration is tested in replicate wells with vehicle controls and positive controls (e.g., U69,593).
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| Animal Protocol |
For in vivo animal studies, ICI-204448 hydrochloride is typically formulated in suitable vehicles and administered via intraperitoneal (i.p.) injection, subcutaneous (s.c.) injection, or intravenous (i.v.) injection. In thermoregulation studies, animals (typically rats) are exposed to cold environments and body temperature is monitored after compound administration. In pain models, nociceptive responses are measured. Dosing regimens vary by study objective. Blood and tissue samples may be collected for pharmacokinetic analysis. All procedures must follow institutional animal care and use committee guidelines.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of ICI-204448 hydrochloride are characteristic of a peripherally acting small-molecule KOR agonist. The compound has a molecular weight of 501.84 and formula C23H27Cl3N2O4. CAS number: 121264-04-8. Purity: 99%. Appearance: white solid with a melting point of 213°C. Storage: typically at room temperature. Solubility: soluble in DMSO and other organic solvents. As a peripherally restricted compound, it has limited blood-brain barrier penetration. Specific pharmacokinetic parameters are reported in the primary literature.
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| Toxicity/Toxicokinetics |
According to available safety information, ICI-204448 hydrochloride is intended for research purposes only and is not for diagnostic or therapeutic use. Standard laboratory safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment (gloves, lab coat, safety goggles). The compound should be handled in a well-ventilated area. Avoid dust formation and inhalation. In case of skin contact, wash with plenty of soap and water. In case of eye contact, rinse cautiously with water for several minutes. No clinical toxicity data are available.
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| References | |
| Additional Infomation |
κ-opioid receptor agonists; structures are described in the first source.
ICI-204448 hydrochloride is a peripherally acting κ-opioid receptor (KOR) agonist. It activates peripheral KOR without crossing the blood-brain barrier, thereby avoiding central side effects such as sedation and dysphoria. In rats, it induces hypothermia in cold environments through peripheral KOR activation. It has been studied for analgesic effects and as a tool for identifying novel KOR-selective ligands. It has a molecular weight of 501.84 and formula C23H27Cl3N2O4. It is for research use only with no regulatory approvals reported. |
| Molecular Formula |
C23H27CL3N2O4
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|---|---|
| Molecular Weight |
501.83
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| Exact Mass |
500.104
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| CAS # |
121264-04-8
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| PubChem CID |
129407
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| Appearance |
Off-white to yellow solid powder
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| Boiling Point |
638.9ºC at 760 mmHg
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| Flash Point |
340.2ºC
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| Vapour Pressure |
3.39E-17mmHg at 25°C
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| LogP |
5.034
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
602
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(C(CN1CCCC1)C2=CC(=CC=C2)OCC(=O)O)C(=O)CC3=CC(=C(C=C3)Cl)Cl.Cl
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| InChi Key |
FNDGLVOYAQNQPE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H26Cl2N2O4.ClH/c1-26(22(28)12-16-7-8-19(24)20(25)11-16)21(14-27-9-2-3-10-27)17-5-4-6-18(13-17)31-15-23(29)30;/h4-8,11,13,21H,2-3,9-10,12,14-15H2,1H3,(H,29,30);1H
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| Chemical Name |
2-[3-[1-[[2-(3,4-dichlorophenyl)acetyl]-methylamino]-2-pyrrolidin-1-ylethyl]phenoxy]acetic acid;hydrochloride
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.9927 mL | 9.9635 mL | 19.9271 mL | |
| 5 mM | 0.3985 mL | 1.9927 mL | 3.9854 mL | |
| 10 mM | 0.1993 mL | 0.9964 mL | 1.9927 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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