| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
μ Opioid Receptor/MOR 0.4 nM (Ki) δ Opioid Receptor/DOR 5.2 nM (Ki) κ Opioid Receptor/KOR 2.0 nM (Ki)
micro, delta, and kappa opioid receptors (pan-opioid antagonist). LY255582 is a centrally active, non-selective opioid receptor antagonist. Its Ki values: micro = 0.4 nM, delta = 5.2 nM, kappa = 2.0 nM. It has the highest affinity for the micro opioid receptor, followed by kappa and delta. |
|---|---|
| ln Vitro |
LY255582 (40 μM, 24-72 h) suppresses the viability of Huh7 and MHCC-97H cells [5].
LY255582 binds to micro, delta, and kappa opioid receptors with Ki values of 0.4 nM (micro), 5.2 nM (delta), and 2.0 nM (kappa). It is a centrally active opioid receptor antagonist (defined as an inverse agonist in a 2011 JPET paper). LY255582 inhibits diet-associated increases in mesolimbic dopamine levels and reduces short- and long-term food intake in rats. It also decreases body weight gain in obese Zucker rats. |
| ln Vivo |
Rats' food intake is reduced by LY255582 (100 μg, icv)[1]. In fed obese Zucker rats, LY255582 (15 mg/kg, subcutaneously, once day) decreases food intake and prevents weight gain[4].
LY255582 inhibits food intake and reduces body weight. It decreases short- and long-term food intake in rats. In obese Zucker rats, LY255582 inhibited weight gain over 30 days. It also inhibits diet-associated increases in mesolimbic dopamine levels. LY255582 is used for the study of obesity, feeding behavior, and the role of endogenous opioid systems in appetite regulation and reward. |
| Enzyme Assay |
Cell-free radioligand binding assays for micro, delta, and kappa opioid receptors are performed using membranes from CHO-K1 cells stably expressing human opioid receptors. For micro: membranes are incubated with [3H]-DAMGO (1-2 nM). For delta: membranes are incubated with [3H]-DPDPE (1-2 nM) or [3H]-naltrindole. For kappa: membranes are incubated with [3H]-U69,593 (0.5-2 nM). Increasing concentrations of LY255582 (0.0001-10,000 nM) are added, and incubations are carried out in 50 mM Tris-HCl (pH 7.4) containing 1 mM EDTA, 5 mM MgCl2, and 0.1% BSA for 60-90 min at 25degC. Bound radioactivity is separated by GF/B filtration. Ki values are calculated using the Cheng-Prusoff equation: Ki (micro) = 0.4 nM, Ki (delta) = 5.2 nM, Ki (kappa) = 2.0 nM.
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| Cell Assay |
Cell-based functional assays (GTPgammaS binding or cAMP accumulation) are performed using CHO cells stably expressing micro, delta, or kappa opioid receptors. For antagonist activity, cells are pre-incubated with LY255582 (0.01-10,000 nM) for 15-30 min, then stimulated with a selective agonist (DAMGO for micro, DPDPE for delta, U50,488 for kappa) in the presence of [35S]-GTPgammaS or forskolin. The degree of agonist-stimulated GTPgammaS binding or inhibition of cAMP accumulation is measured. LY255582 dose-dependently antagonizes agonist-induced effects at all three receptor subtypes, with highest potency at micro, consistent with binding affinities. It may also show inverse agonist activity at micro receptors in certain assays (e.g., constitutive activity systems).
|
| Animal Protocol |
Animal/Disease Models: STZ-induced diabetic mice[1]
Doses: 100, 10 and 1 μg Route of Administration: icv Experimental Results: diminished food at 100, 10 and 1 μg by 76, 62 and 29%. Feeding studies: Male Sprague-Dawley rats (food-deprived for 18-24 h) receive LY255582 (0.1-10 mg/kg) via oral gavage, intraperitoneal (i.p.) injection, or subcutaneous (s.c.) injection 30-60 min before access to food. Food intake (g) is measured at 1, 2, 4, and 24 hours post-refeeding. LY255582 significantly reduces short-term (1-4 h) and long-term (24 h) food intake in a dose-dependent manner. Body weight studies: Obese Zucker rats receive LY255582 daily (e.g., 1-10 mg/kg s.c. or p.o.) for up to 30 days. Body weight is measured daily. LY255582 inhibits weight gain compared to vehicle-treated controls. For microdialysis studies: rats with implanted microdialysis probes in the nucleus accumbens receive LY255582 (i.p. or s.c.) and then are allowed access to palatable food. Dialysate dopamine levels are measured by HPLC-ECD. LY255582 inhibits diet-associated increases in mesolimbic dopamine levels. |
| ADME/Pharmacokinetics |
LY255582 is centrally active and, therefore, crosses the blood-brain barrier. The molecular weight is 345.52 (C22H35NO2). CAS# 119193-09-8. Purity ≥98%. Storage: -20degC, protected from light, dry. Solubility: DMSO (10-50 mg/mL). LY255582 is an opioid antagonist and may have acceptable oral bioavailability, but exact PK parameters (t1/2, Cmax, AUC, F%) are not reported. It is likely metabolized in the liver by CYP enzymes. The compound exhibits dose-dependent effects on feeding behavior over several hours after systemic administration, suggesting a pharmacologically relevant half-life (possibly 2-6 hours in rodents).
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for LY255582. In published animal studies at doses up to 10 mg/kg (acute or repeated dosing), no signs of acute toxicity (seizures, respiratory depression, or mortality) were observed. As an opioid antagonist, it may precipitate withdrawal symptoms in opioid-dependent subjects. Weight loss and reduced food intake are the primary pharmacodynamic effects, which are intended for obesity research. Standard toxicological assessments (hERG, Ames, repeat-dose toxicity in rats/dogs) have not been performed. LY255582 has not progressed to clinical trials for obesity. Not FDA-approved. For research use only.
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| References |
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| Additional Infomation |
Other information: LY255582 is a research compound (CAS# 119193-09-8), not FDA-approved. It is a potent, centrally active pan-opioid receptor antagonist with Ki values of 0.4 nM (micro), 5.2 nM (delta), and 2.0 nM (kappa). It is widely used as a research tool to study the role of endogenous opioid systems in feeding behavior, obesity, body weight regulation, addiction, and reward. It is also used to investigate the involvement of opioid receptors in stress responses and mood regulation. For research use only.
|
| Molecular Formula |
C22H35NO2
|
|---|---|
| Molecular Weight |
345.52
|
| Exact Mass |
345.267
|
| CAS # |
119193-09-8
|
| PubChem CID |
9906198
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.26
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
25
|
| Complexity |
409
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
C[C@H]1CN(CC[C@@]1(C)C2=CC(=CC=C2)O)CC[C@@H](C3CCCCC3)O
|
| InChi Key |
LVVHEFJXPXAUDD-BULFRSBZSA-N
|
| InChi Code |
InChI=1S/C22H35NO2/c1-17-16-23(13-11-21(25)18-7-4-3-5-8-18)14-12-22(17,2)19-9-6-10-20(24)15-19/h6,9-10,15,17-18,21,24-25H,3-5,7-8,11-14,16H2,1-2H3/t17-,21-,22+/m0/s1
|
| Chemical Name |
3-[(3R,4R)-1-[(3S)-3-cyclohexyl-3-hydroxypropyl]-3,4-dimethylpiperidin-4-yl]phenol
|
| 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)
|
| 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 | 2.8942 mL | 14.4709 mL | 28.9419 mL | |
| 5 mM | 0.5788 mL | 2.8942 mL | 5.7884 mL | |
| 10 mM | 0.2894 mL | 1.4471 mL | 2.8942 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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