| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
LY-3130481 targets the AMPA receptor, a glutamate-gated ion channel that mediates fast excitatory neurotransmission in the central nervous system. The compound is a TARP γ-8-dependent AMPA receptor antagonist, meaning its activity requires the presence of the auxiliary subunit TARP γ-8. It selectively inhibits AMPA/TARP γ-8 with an IC50 of 65 nM.
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| ln Vitro |
In vitro, LY-3130481 selectively inhibits AMPA receptors that are associated with TARP γ-8 with an IC50 of 65 nM. The compound's TARP γ-8-dependent mechanism provides selectivity for specific AMPA receptor populations, potentially reducing the motor impairment associated with non-TARP-dependent AMPA receptor antagonists.
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| ln Vivo |
In vivo, LY-3130481 is fully protective against pentylenetetrazole-induced convulsions in rats without the motor impairment associated with non-TARP-dependent AMPA receptor antagonists. The compound has demonstrated anticonvulsant, antiepileptic, and pain-relieving effects in preclinical models. It is orally available, supporting its potential for clinical development.
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| Enzyme Assay |
In vitro receptor binding assays for AMPA receptor antagonism involve incubating membranes from cells expressing AMPA receptors with or without TARP γ-8 with radiolabeled AMPA or glutamate and varying concentrations of LY-3130481. Non-specific binding is determined using excess unlabeled ligand. Bound radioactivity is measured by scintillation counting to calculate IC50 values.
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| Cell Assay |
Cellular assays are performed using cells expressing AMPA receptors with or without TARP γ-8. Cells are treated with LY-3130481 at various concentrations, and AMPA-induced calcium influx or current is measured using fluorescence-based calcium indicators or patch-clamp electrophysiology. The TARP γ-8 dependence of the compound's activity is confirmed by comparing inhibition in cells with and without TARP γ-8 expression.
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| Animal Protocol |
In vivo studies are conducted in rodent models of epilepsy and pain. LY-3130481 is administered orally or intraperitoneally at various doses. In the pentylenetetrazole-induced seizure model, the compound's ability to protect against convulsions is assessed. Motor impairment is evaluated using rotarod or open field tests to confirm the lack of motor side effects. Pain-relieving effects are assessed in models of neuropathic or inflammatory pain.
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| ADME/Pharmacokinetics |
LY-3130481 (molecular weight 383.42, formula C₁₉H₁₇N₃O₄S) is a small-molecule compound. It is orally available and soluble in DMSO. The compound is typically stored at -20°C. Its physicochemical properties support oral bioavailability and favorable drug-like characteristics.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies have evaluated LY-3130481 in animal models. As a TARP γ-8-dependent AMPA receptor antagonist, its toxicity profile is expected to be improved compared to non-selective AMPA receptor antagonists due to reduced motor impairment. The compound has demonstrated a favorable safety profile in preclinical studies.
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| References | |
| Additional Infomation |
LY-3130481 (CERC-611) is the first TARP γ-8-dependent AMPA receptor antagonist. Its mechanism involves selective inhibition of AMPA receptors that are associated with the auxiliary subunit TARP γ-8, providing a unique approach to modulating glutamatergic neurotransmission. The compound has demonstrated anticonvulsant and pain-relieving effects without the motor side effects associated with traditional AMPA receptor antagonists, making it a promising candidate for epilepsy and pain indications.
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| Molecular Formula |
C19H18N4O3S
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|---|---|
| Molecular Weight |
382.4362
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| Exact Mass |
382.109
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| CAS # |
1610802-47-5
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| PubChem CID |
74223604
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
525
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| Defined Atom Stereocenter Count |
1
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| SMILES |
S1C(N([H])C2C([H])=C([H])C(=C([H])C1=2)[C@]([H])(C([H])([H])[H])C1C([H])=C([H])N(C2C([H])=C([H])C(=C([H])N=2)OC([H])([H])C([H])([H])O[H])N=1)=O
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| InChi Key |
HLTKOFPQDKJCAN-LBPRGKRZSA-N
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| InChi Code |
InChI=1S/C19H18N4O3S/c1-12(13-2-4-16-17(10-13)27-19(25)21-16)15-6-7-23(22-15)18-5-3-14(11-20-18)26-9-8-24/h2-7,10-12,24H,8-9H2,1H3,(H,21,25)/t12-/m0/s1
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| Chemical Name |
(S)-6-(1-(1-(5-(2-hydroxyethoxy)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one
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| Synonyms |
LY3130481; LY-3130481; LY 3130481; CERC-611; CERC611; CERC 611.
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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) |
DMSO : ~250 mg/mL (~653.70 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.44 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 20.8 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: ≥ 2.08 mg/mL (5.44 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 20.8 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: ≥ 2.08 mg/mL (5.44 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 | 2.6148 mL | 13.0739 mL | 26.1479 mL | |
| 5 mM | 0.5230 mL | 2.6148 mL | 5.2296 mL | |
| 10 mM | 0.2615 mL | 1.3074 mL | 2.6148 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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