LY3130481 (also known as CERC-611) is a novel and potent α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist t that is dependent upon transmembrane AMPA receptor regulatory protein (TARP) γ-8, it selective inhibits AMPA/TARP γ-8 with an IC50 of 65 nM. LY3130481 is fully protective against pentylenetetrazole-induced convulsions in rats without the motor impairment associated with non-TARP-dependent AMPA receptor antagonists. Compound (−)-25 could be utilized to provide proof of concept for antiepileptic efficacy with reduced motor side effects in patients.
Physicochemical Properties
| Molecular Formula | C19H18N4O3S |
| Molecular Weight | 382.4362 |
| Exact Mass | 382.109 |
| CAS # | 1610802-47-5 |
| PubChem CID | 74223604 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 2.5 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 27 |
| Complexity | 525 |
| Defined Atom Stereocenter Count | 1 |
| 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 |
| InChi Key | HLTKOFPQDKJCAN-LBPRGKRZSA-N |
| 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 |
| Chemical Name | (S)-6-(1-(1-(5-(2-hydroxyethoxy)pyridin-2-yl)-1H-pyrazol-3-yl)ethyl)benzo[d]thiazol-2(3H)-one |
| Synonyms | LY3130481; LY-3130481; LY 3130481; CERC-611; CERC611; CERC 611. |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| References |
[1]. Discovery of the First α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Antagonist Dependent upon Transmembrane AMPA Receptor Regulatory Protein (TARP) γ-8. J Med Chem. 2016 May 26;59(10):4753-68. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~250 mg/mL (~653.70 mM) |
| 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. 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. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |