| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
LY2444296 primarily targets the kappa opioid receptor (KOPR), a G protein-coupled receptor involved in the regulation of pain, stress, mood, and addiction. It acts as a high-affinity and selective antagonist with a Ki of approximately 1 nM. By blocking KOPR, LY2444296 modulates the effects of endogenous dynorphins and prevents KOPR-mediated signaling. This makes it a valuable tool for exploring neuropsychiatric disorders, stress-related pathology, and addiction biology.
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| ln Vitro |
In vitro, LY2444296 functions as a potent, selective KOPR antagonist with a Ki of approximately 1 nM. Its activity is typically measured using radioligand binding assays in membrane preparations expressing recombinant KOPR. Functional assays such as cAMP accumulation or β-arrestin recruitment are used to assess antagonist activity. The compound's selectivity for KOPR over other opioid receptors (mu and delta) is evaluated. The short-acting nature of the antagonist is characterized in functional assays.
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| ln Vivo |
LY2444296 showed anxiolytic-like effects in the EPM test [1]. LY2444296 (3 mg/kg; i.p.; 30 minutes before U69,593 administration) inhibits behavioral and neuroendocrine effects caused by the reference kappa agonist U69,593 in cocaine-naïve rats [2]. LY2444296 lowers anxiety-like and depressive-like behaviors and CORT release in rats assessed following chronic self-administration of cocaine, but not in cocaine-naïve rats [2]
In vivo, LY2444296 exhibits anti-anxiety-like effects in the elevated plus maze (EPM) test. It reduces anxiety-like and depressive-like behaviors, as well as CORT release, in rats tested after chronic extended access cocaine self-administration. The compound is orally bioavailable and short-acting. Its unique pharmacological profile makes it a valuable tool for exploring neuropsychiatric disorders, stress-related pathology, and addiction biology. |
| Enzyme Assay |
Cell-free assays for LY2444296 involve evaluating its binding affinity to KOPR. Radioligand binding assays are performed using membrane preparations from cells expressing recombinant human KOPR. LY2444296 is incubated with membranes and a radiolabeled KOPR ligand. Competition binding experiments determine Ki values (approximately 1 nM). Selectivity is assessed by testing against mu and delta opioid receptors. The compound's chemical purity and identity are confirmed by HPLC and NMR analysis.
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| Cell Assay |
In vitro cellular assays for LY2444296 typically involve treating cells expressing KOPR with various concentrations of the compound. Functional assays such as cAMP accumulation or β-arrestin recruitment are used to measure KOPR activity. The compound's ability to block KOPR-mediated signaling is assessed. IC50 or Ki values are determined from dose-response curves. Cytotoxicity is evaluated using standard cell viability assays. The compound is typically dissolved in DMSO and diluted in cell culture medium.
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| Animal Protocol |
Animal/Disease Models: Adult male SD (SD (Sprague-Dawley)) rat (240–250 g) [2]
Doses: 3 mg/kg Route of Administration: intraperitoneal (ip) injection; 30 minutes before administration of U69,593 Experimental Results: Prevention of U69,593 effects on the untreated Behavioral and neuroendocrine effects in rats exposed to cocaine. In vivo animal studies for LY2444296 are conducted in rat models of anxiety, depression, and addiction. The compound is administered orally or via other routes. Behavioral assays including the elevated plus maze (EPM) test are used to assess anxiety-like behaviors. Depressive-like behaviors are assessed using forced swim test or other assays. CORT (corticosterone) release is measured in plasma. Pharmacokinetic parameters are determined from plasma samples collected at various time points. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of LY2444296 include a molecular weight of 408.44 g/mol and molecular formula C24H22F2N2O2. The compound is orally bioavailable and short-acting. As a small molecule antagonist, it is expected to have good oral bioavailability and tissue penetration, including brain penetration. Detailed ADME parameters such as half-life, Cmax, and AUC are not extensively reported in the available literature. The compound is typically stored at appropriate conditions as a research reagent.
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| Toxicity/Toxicokinetics |
The toxicity profile of LY2444296 has been characterized in preclinical studies. As a KOPR antagonist, potential toxicities may include effects on mood, pain perception, and stress responses. Standard toxicology studies would include acute and sub-chronic toxicity assessments in rodent models. The compound is intended for research use only and not for therapeutic applications in humans. Standard safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
LY2444296 (FP3FBZ) is an orally bioavailable, high-affinity, and selective short-acting kappa opioid receptor (KOPR) antagonist with a Ki of approximately 1 nM. It exhibits anti-anxiety-like effects in the EPM test and reduces anxiety-like and depressive-like behaviors in rats. LY2444296 is a valuable research tool for studying neuropsychiatric disorders, stress, and addiction. It has not entered clinical trials and is strictly for research purposes.
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| Molecular Formula |
C24H22F2N2O2
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|---|---|
| Molecular Weight |
408.4405
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| Exact Mass |
408.164
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| CAS # |
1346133-11-6
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| PubChem CID |
56655502
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
569
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1=C([H])C([H])=C([H])C(=C1[H])[C@]1([H])C([H])([H])C([H])([H])C([H])([H])N1C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])OC1C([H])=C([H])C(C(N([H])[H])=O)=C([H])C=1F
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| InChi Key |
WHHMECUDUQRPJT-QFIPXVFZSA-N
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| InChi Code |
InChI=1S/C24H22F2N2O2/c25-19-4-1-3-17(13-19)22-5-2-12-28(22)15-16-6-9-20(10-7-16)30-23-11-8-18(24(27)29)14-21(23)26/h1,3-4,6-11,13-14,22H,2,5,12,15H2,(H2,27,29)/t22-/m0/s1
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| Chemical Name |
3-fluoro-4-[4-[[(2S)-2-(3-fluorophenyl)pyrrolidin-1-yl]methyl]phenoxy]benzamide
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| Synonyms |
LY2444296; LY-2444296
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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) |
Ethanol : ~27.5 mg/mL (~67.33 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (6.73 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 2.75 mg/mL (6.73 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4483 mL | 12.2417 mL | 24.4834 mL | |
| 5 mM | 0.4897 mL | 2.4483 mL | 4.8967 mL | |
| 10 mM | 0.2448 mL | 1.2242 mL | 2.4483 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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