| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Ki: 64 nM (MOR), 118 nM (σ1R)[1]
micro-opioid receptor (MOR) and σ1 receptor (σ1R). EST73502 is a MOR agonist (Ki = 64 nM) and a σ1R antagonist (Ki = 118 nM). It exhibits selectivity for these two targets over related receptors. |
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| ln Vitro |
EST73502 binds to MOR with a Ki of 64 nM and to σ1R with a Ki of 118 nM. As a MOR agonist, it activates G-protein signaling and reduces cAMP accumulation in MOR-expressing cells. As a σ1R antagonist, it blocks σ1R-mediated signaling, potentially reducing neuropathic pain and preventing opioid-induced tolerance and dependence. EST73502 displays antinociceptive activity.
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| ln Vivo |
In the paw pressure test, EST73502 monohydrochloride (10–40 mg/kg; po) exhibits a dose-response analgesic effect with a maximum of 64% and an EC50 of 14 mg/kg in CD1 male mice[1]. In male CD1 mice, mechanical allodynia caused by partial sciatic nerve ligation (PSNL) is lessened by EST73502 monohydrochloride (5 mg/kg; ip; twice a day; for 10 days)[1].
EST73502 monohydrochloride displays antinociceptive activity. In the paw pressure test in male CD1 mice, EST73502 monohydrochloride (10-40 mg/kg; p.o.) exhibits dose-response analgesic effects with a maximum effect of 64% and an EC50 of 14 mg/kg. In male CD1 mice with partial sciatic nerve ligation (PSNL), EST73502 monohydrochloride (5 mg/kg; i.p.; twice daily for 10 days) attenuates mechanical allodynia, reaching a maximal effect of 56%. These studies confirm its efficacy in acute and neuropathic pain models. |
| Enzyme Assay |
Cell-free MOR and σ1R binding assays are performed using membrane preparations from CHO cells stably expressing human MOR or σ1R. For MOR: membranes are incubated with [3H]-DAMGO (1-2 nM) and increasing concentrations of EST73502 (0.01-10,000 nM) in 50 mM Tris-HCl (pH 7.4) containing 5 mM MgCl2 and 0.1% BSA for 60 min at 25degC. For σ1R: membranes are incubated with [3H]-pentazocine (1-5 nM) under similar conditions. Bound radioactivity is separated by GF/B filtration. Ki values are calculated by nonlinear regression. Ki values: MOR = 64 nM, σ1R = 118 nM.
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| Cell Assay |
Functional MOR agonism: CHO cells expressing human MOR and a CRE-luciferase reporter are treated with EST73502 (0.1-10,000 nM) for 5 hours at 37degC. Luciferase activity is measured. EC50 for MOR-mediated cAMP inhibition is determined. Functional σ1R antagonism: HEK293 cells expressing σ1R are pre-incubated with EST73502 (0.1-10,000 nM) for 15 min, then stimulated with a σ1R agonist (e.g., PRE-084). σ1R antagonist activity is measured by its ability to block agonist-induced calcium mobilization or neurite outgrowth. EST73502 shows antagonist activity at σ1R with an appropriate IC50.
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| Animal Protocol |
Animal/Disease Models: Male CD1 mice, PSNL model[1]
Doses: 5 mg /kg Route of Administration: intraperitoneal (ip) injection, twice a day, for 10 days Experimental Results: Attenuated the expression of mechanical allodynia induced by PSNL, reaching a maximal effect of 56%. Acute pain model (paw pressure test): Male CD1 mice (25-30 g) receive EST73502 monohydrochloride orally (10, 20, 40 mg/kg) 60 min before testing. Mechanical nociceptive threshold (in grams) is measured using an analgesiometer (Ugo Basile). The percentage of maximal possible effect (%MPE) is calculated. ED50 is determined. Neuropathic pain model (PSNL): Male CD1 mice undergo partial sciatic nerve ligation. After 14 days (when allodynia is established), EST73502 monohydrochloride (5 mg/kg) is administered i.p. twice daily for 10 days. Mechanical allodynia is measured using von Frey filaments. The paw withdrawal threshold (PWT) is recorded. EST73502 attenuates PSNL-induced mechanical allodynia with a maximal effect of 56%. |
| ADME/Pharmacokinetics |
EST73502 monohydrochloride is orally active and penetrates the blood-brain barrier (BBB). Molecular weight: 388.88 (C19H27ClF2N2O2). CAS# 2535970-65-9. Purity ≥98%. Storage: powder at -20degC for 3 years, in solvent at -80degC for 6 months. The free base CAS# is 1838622-25-5. Solubility: DMSO, ethanol, and water; formulations may be prepared with PEG400, Tween-80, or saline. PK parameters (t1/2, Cmax, AUC, oral bioavailability) in rodents have not been fully characterized in published literature.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for EST73502 monohydrochloride. In acute and repeated-dose studies in mice (10-40 mg/kg orally, or 5 mg/kg i.p. twice daily for 10 days), no overt signs of toxicity (behavioral changes, weight loss, or mortality) were observed. The dual MOR agonist/σ1R antagonist mechanism is designed to reduce typical opioid-related adverse effects such as tolerance, physical dependence, and respiratory depression. However, comprehensive toxicological assessments have not been published. The compound has not entered clinical trials.
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| References | |
| Additional Infomation |
Other information: EST73502 monohydrochloride is a research compound (CAS 2535970-65-9) not FDA-approved. It is a dual MOR agonist/σ1R antagonist developed for pain therapy. The simultaneous activation of MOR and antagonism of σ1R is hypothesized to produce effective antinociception while reducing opioid-induced tolerance, reward, and other side effects. EST73502 is useful for studying the interactions between opioid and sigma receptor systems in pain, addiction, and neuropsychiatric disorders. For research use only.
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| Molecular Formula |
C19H27CLF2N2O2
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| Molecular Weight |
388.879691362381
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| Exact Mass |
388.172
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| CAS # |
2535970-65-9
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| Related CAS # |
EST73502;1838622-25-5
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| PubChem CID |
153535293
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| Appearance |
White to off-white solid powder
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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 |
4
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| Heavy Atom Count |
26
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| Complexity |
468
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| Defined Atom Stereocenter Count |
1
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| SMILES |
Cl.FC1C=CC(=CC=1CCN1CCC2(CN(CC)C([C@@H](C)O2)=O)CC1)F
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| InChi Key |
WZJJIHSIBMZUIN-PFEQFJNWSA-N
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| InChi Code |
InChI=1S/C19H26F2N2O2.ClH/c1-3-23-13-19(25-14(2)18(23)24)7-10-22(11-8-19)9-6-15-12-16(20)4-5-17(15)21;/h4-5,12,14H,3,6-11,13H2,1-2H3;1H/t14-;/m1./s1
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| Chemical Name |
(2R)-9-[2-(2,5-difluorophenyl)ethyl]-4-ethyl-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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: 50 mg/mL (128.57 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.43 mM) (saturation unknown) in 10% DMSO + 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 25.0 mg/mL clear DMSO 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5715 mL | 12.8574 mL | 25.7149 mL | |
| 5 mM | 0.5143 mL | 2.5715 mL | 5.1430 mL | |
| 10 mM | 0.2571 mL | 1.2857 mL | 2.5715 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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