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| 5mg |
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Purity: ≥98%
LY3020371 HCl is a novel, potent, selective mGlu2/3 (metabotropic glutamate 2/3) receptor antagonist with Ki of 5.3 and 2.5 nM, potently blocks cAMP formation with IC50 of 16.2 nM. LY3020371 hydrochloride exerts an antidepressant-like signature in vivo. The novel mGlu2/3 receptor antagonist, LY3020371, has been shown to produce antidepressant-like effects comparable to that of the clinically-effective antidepressant ketamine. In preclinical toxicology studies of 14day dosing of doses up to 1000mg/kg, i.v. in rats and up to 500m/kg, i.v. in Cynomologous monkeys, LY3020371 produced uM plasma exposures without producing critical toxicological findings. It is concluded that LY3020371 does not recapitulate the motor, cognitive, subjective, neurochemical, electrophysiological, or toxicological findings reported with ketamine. Thus, LY3020371 possesses both the efficacy signatures of a rapidly-acting antidepressant and a safety profile enabling proof of concept studies in patients.
| ln Vitro |
The mGlu2/3 agonist ligand [3H]-459477 is displaced by LY3020371 hydrochloride (LY3020371.HCl) with a high degree of affinity (hmGlu2 Ki=5.26 nM; hmGlu3 Ki=2.50 nM). [1]. Hydrochloromethyl LY3020371 (LY3020371.HCl) (0.1 nM-100 μM; 1 h) potently inhibits the production of cAMP induced by forskolin and mGlu2/3 agonist (DCG-IV) (IC50=16.2 nM). Cells expressing hmGlu3 experience this impact (IC50=6.21 nM).[1]. Both intact hippocampal slice preparations (IC50=46 nM) and agonist-inhibited spontaneous Ca2+ oscillations (IC50=34 nM) are blocked by LY3020371 hydrochloride (LY3020371.HCl) [1].
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| ln Vivo |
The intravenous injection of LY3020371 hydrochloride (LY3020371.HCl) at a dose of 3–15 mg/kg in rats is expected to produce drug levels in the cerebrospinal fluid that effectively block mGlu2/3 receptors [1]. The intraperitoneal injection of LY3020371 hydrochloride (3 mg/kg, 10 mg/kg; 2 hours) significantly reduces light NREM sleep in Wistar rats by having a wake-promoting effect [3].
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| References |
[1]. Witkin JM, et al. In vitro pharmacological and rat pharmacokinetic characterization of LY3020371, a potent and selective mGlu2/3 receptor antagonist. Neuropharmacology. 2017 Mar 15;115:100-114.
[2]. Witkin JM, et al. Preclinical predictors that the orthosteric mGlu2/3 receptor antagonist LY3020371 will not engender ketamine-associated neurotoxic, motor, cognitive, subjective, or abuse-liability-related effects. Pharmacol Biochem Behav. 2017 Apr;155:4 [3]. Wood CM, et al. Investigating the role of mGluR2 versus mGluR3 in antipsychotic-like effects, sleep-wake architecture and network oscillatory activity using novel Han Wistar rats lacking mGluR2 expression. Neuropharmacology. 2018 Sep 15;140:246-259. |
| Molecular Formula |
C15H16CLF2NO5S
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|---|---|
| Molecular Weight |
395.806049346924
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| CAS # |
1377615-44-5
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| Related CAS # |
LY3020371;1377615-75-2
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| SMILES |
O=C([C@@]1(N)[C@]2([H])[C@@H](C(O)=O)[C@]2([H])[C@H](O)[C@H]1CSC3=CC=C(F)C(F)=C3)O.[H]Cl
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| Synonyms |
LY-3020371; LY3020371; LY 3020371
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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 : ~250 mg/mL (~631.62 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.26 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 (5.26 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 (5.26 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 | 2.5265 mL | 12.6323 mL | 25.2646 mL | |
| 5 mM | 0.5053 mL | 2.5265 mL | 5.0529 mL | |
| 10 mM | 0.2526 mL | 1.2632 mL | 2.5265 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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