| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Mirogabalin targets the α2δ-1 and α2δ-2 subunits of voltage-gated calcium channels. Mirogabalin besylate is an oral selective α₂δ-1 subunit ligand that binds to the α₂δ-1 subunit of voltage-gated calcium channels, reducing calcium influx, inhibiting neuronal hyperexcitability and pain signal transmission. The compound has Kd values of 13.5 nM, 22.7 nM, 27 nM, and 47.6 nM for human α2δ-1, human α2δ-2, rat α2δ-1, and rat α2δ-2, respectively. By binding to the α2δ subunit, mirogabalin modulates the function of voltage-gated calcium channels, reducing the release of excitatory neurotransmitters such as glutamate, substance P, and calcitonin gene-related peptide. This mechanism contributes to its analgesic effects in neuropathic pain. Mirogabalin is a third-generation gabapentinoid with improved potency and selectivity compared to earlier compounds.
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| ln Vitro |
Mirogabalin besylate is a ligand for voltage-gated calcium channel's α2δ subunit. Rat α2δ-1, rat α2δ-2, human α2δ-1, and rat α2δ have Kd values of 13.5 nM, 22.7 nM, 27 nM, and 47.6 nM, in that order. is -2. In rat cortical brain homogenate, mirogabalin binds with affinity to the gabapentin binding site, with an IC50 value of 16.0 nM. At 50 μM, no additional receptors, channels, transporters, or enzymes are affected by milopalin [1].
In vitro, mirogabalin demonstrates potent and selective binding to the α2δ subunit of voltage-gated calcium channels. The compound has Kd values of 13.5 nM, 22.7 nM, 27 nM, and 47.6 nM for human α2δ-1, human α2δ-2, rat α2δ-1, and rat α2δ-2, respectively. Mirogabalin is a highly potent and selective α2δ-1 ligand for the α2δ-1 subunit of the voltage-sensitive calcium channel complex in the central nervous system. In cellular assays, mirogabalin's effects on calcium influx and neurotransmitter release can be assessed. The compound's selectivity for α2δ subunits over other calcium channel subunits contributes to its efficacy and safety profile. Mirogabalin's in vitro activity supports its use as an analgesic for neuropathic pain. |
| ln Vivo |
Rats with a partial sciatic nerve ligation model showed a dose-dependent substantial rise in AUC0-8 hour values when treated with mirogabalin besylate (3 and 10 mg/kg). With estimated ED50s of 4.4, 3.1, and < 2.5 mg/kg, and day 5, milopalin (2.5, 5 and 10 mg/kg) resulted in a significant and dose-dependent rise in AUC0-12 hour values and increased analgesia. Furthermore, rotarod performance and locomotor activity were not significantly affected by the oral administration of milopaline besylate at 3 or 10 mg/kg, but they were considerably suppressed by the oral administration of 10, 30, and 100 mg/kg. Rats responded favorably to 30 and 100 mg/kg [1].
In vivo, mirogabalin demonstrates potent and sustained analgesic effects in various animal models of pain. Mirogabalin has potent and sustained analgesic effects with an ED₅₀ of 2.5 mg/kg. The compound is developed for the treatment of neuropathic pain conditions, such as diabetic peripheral neuropathy and postherpetic neuralgia. Mirogabalin is a calcium channel blocker with analgesic effects. The compound's in vivo efficacy in pain models supports its clinical use for neuropathic pain. Mirogabalin has been approved in Japan for the treatment of neuropathic pain. |
| Enzyme Assay |
In vitro binding assays for mirogabalin employ radioligand displacement techniques using membrane preparations from cells or tissues expressing α2δ subunits. The assay involves incubating mirogabalin at varying concentrations with the membrane preparation and a fixed concentration of a radiolabeled α2δ ligand, such as [³H]-gabapentin. Following incubation, bound and free radioligand are separated by rapid filtration, and radioactivity is measured. Non-specific binding is determined in the presence of a high concentration of an unlabeled α2δ ligand. Binding affinity (Kd) values are calculated from saturation or competition curves using nonlinear regression analysis. For functional assays, cells expressing voltage-gated calcium channels are used, and calcium influx is measured using fluorescent indicators.
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| Cell Assay |
In vitro cellular assays for mirogabalin employ neuronal cell lines or primary neurons expressing voltage-gated calcium channels. Cells are cultured in appropriate media and treated with mirogabalin at various concentrations. Calcium influx is measured using fluorescent indicators such as Fura-2 or Fluo-4 following depolarization. Neurotransmitter release is measured by HPLC or ELISA. The compound's effects on cell viability and proliferation can be assessed using standard cytotoxicity assays. The compound's selectivity for α2δ subunits can be confirmed by testing against other calcium channel subunits.
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| Animal Protocol |
In vivo animal experiments for mirogabalin employ models of neuropathic pain. For studies investigating neuropathic pain, animal models such as the spinal nerve ligation model, streptozotocin-induced diabetic neuropathy model, or postherpetic neuralgia model are used. Mirogabalin is administered orally, and pain behaviors such as mechanical allodynia and thermal hyperalgesia are assessed. For pharmacokinetic studies, blood samples are collected at various time points, and mirogabalin concentrations are measured by LC-MS/MS. Dosing regimens vary depending on the experimental objectives.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of mirogabalin have been characterized in clinical studies. Mirogabalin is rapidly absorbed, with a median time to maximum plasma concentration of 1 hour, and rapidly eliminated, with a mean elimination half-life of 2 to 3 hours. Single-dose mirogabalin pharmacokinetic parameters were comparable between Asian and white subjects. Exposure increased proportionally as mirogabalin. Maximum plasma concentration is achieved in less than 1 hour. The plasma protein binding is relatively low, at less than 25%. Mirogabalin is primarily excreted unchanged in the urine, and the administration dose should be adjusted according to renal function.
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| Toxicity/Toxicokinetics |
The toxicity profile of mirogabalin is consistent with that of gabapentinoids. Common adverse effects include somnolence, dizziness, headache, and peripheral edema. The compound should be used with caution in patients with renal impairment, as dose adjustment is required. Mirogabalin has been approved in Japan for the treatment of neuropathic pain. The compound's safety in pregnancy and lactation has not been established, and its use should be guided by clinical judgment.
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| References | |
| Additional Infomation |
Mirogabalin besylate is a selective and orally available ligand for the α2δ subunit of voltage-gated calcium channels. It binds to the α₂δ-1 subunit, reducing calcium influx, inhibiting neuronal hyperexcitability and pain signal transmission. The compound has Kd values of 13.5 nM, 22.7 nM, 27 nM, and 47.6 nM for human α2δ-1, human α2δ-2, rat α2δ-1, and rat α2δ-2, respectively. Mirogabalin is rapidly absorbed with a median T_max of 1 hour and a mean elimination half-life of 2 to 3 hours. It has potent and sustained analgesic effects (ED₅₀ = 2.5 mg/kg). Mirogabalin besylate has a molecular weight of 367.46 and a molecular formula of C₁₈H₂₅NO₅S. It is developed for neuropathic pain.
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| Molecular Formula |
C18H25NO5S
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|---|---|
| Molecular Weight |
367.46
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| Exact Mass |
367.145
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| CAS # |
1138245-21-2
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| Related CAS # |
1138245-21-2 (besylate);1138245-13-2;
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| PubChem CID |
81689826
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
494
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CCC1=C[C@@H]2[C@H](C1)C[C@@]2(CC(=O)O)CN.C1=CC=C(C=C1)S(=O)(=O)O
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| InChi Key |
2-((1R,5S,6S)-6-(aminomethyl)-3-ethylbicyclo[3.2.0]hept-3-en-6-yl)acetic acid compound with benzenesulfonic acid (1
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| InChi Code |
OKJXJRVWXYRSAN-TXULWXBWSA-N
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| Chemical Name |
DS-5565 DS 5565 DS5565 A-2000700 Mirogabalin Mirogabalin besylate.
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| Synonyms |
DS-5565 DS 5565 DS5565 A-2000700A2000700A 2000700
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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 : ~125 mg/mL (~340.17 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.58 mg/mL (7.02 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 25.8 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: ≥ 2.58 mg/mL (7.02 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 25.8 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: ≥ 2.58 mg/mL (7.02 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 | 2.7214 mL | 13.6069 mL | 27.2138 mL | |
| 5 mM | 0.5443 mL | 2.7214 mL | 5.4428 mL | |
| 10 mM | 0.2721 mL | 1.3607 mL | 2.7214 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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