| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
LY3020371 HCl targets the metabotropic glutamate 2/3 receptors (mGlu2/3), which are group II metabotropic glutamate receptors. It acts as a potent and selective antagonist with Ki values of 5.3 nM for mGlu2 and 2.5 nM for mGlu3. By blocking mGlu2/3 receptors, the compound inhibits the receptor-mediated suppression of cAMP formation with an IC50 of 16.2 nM.
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| 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].
In vitro, LY3020371 HCl potently blocks cAMP formation with an IC50 of 16.2 nM. The compound demonstrates high affinity for mGlu2 (Ki = 5.3 nM) and mGlu3 (Ki = 2.5 nM). By antagonizing mGlu2/3 receptors, it prevents the receptor-mediated inhibition of adenylyl cyclase, leading to increased cAMP levels and modulation of downstream signaling pathways. |
| 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].
In vivo, LY3020371 HCl exerts antidepressant-like effects. The compound has been evaluated in preclinical models of depression, demonstrating efficacy in behavioral tests such as the forced swim test or tail suspension test. Its ability to block mGlu2/3 receptors and modulate glutamatergic neurotransmission contributes to its antidepressant-like activity. |
| Enzyme Assay |
In vitro receptor binding assays for mGlu2/3 antagonism involve incubating membranes from cells expressing human recombinant mGlu2 or mGlu3 receptors with radiolabeled ligands and varying concentrations of LY3020371 HCl. Functional assays measure the compound's ability to block agonist-induced inhibition of forskolin-stimulated cAMP accumulation in cells expressing mGlu2 or mGlu3 receptors. Ki and IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cellular assays are performed using cell lines expressing human recombinant mGlu2 or mGlu3 receptors (e.g., CHO or HEK-293 cells). Cells are treated with LY3020371 HCl at various concentrations in the presence of a group II mGlu receptor agonist and forskolin. Intracellular cAMP levels are measured using a luminescent or fluorescent cAMP detection kit. The compound's antagonist potency is determined by measuring the reversal of agonist-induced inhibition of cAMP accumulation.
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| Animal Protocol |
In vivo studies are conducted in rodent models of depression, such as the forced swim test or tail suspension test. LY3020371 HCl is administered intraperitoneally or orally at various doses. Antidepressant-like effects are assessed by measuring reductions in immobility time. Brain tissue is collected for biomarker analysis to confirm target engagement and modulation of glutamatergic signaling.
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| ADME/Pharmacokinetics |
LY3020371 HCl (molecular weight 392.83, formula C₁₉H₂₁ClN₂O₅) is a small-molecule compound. It is soluble in DMSO and water. The compound is typically stored at -20°C. Its physicochemical properties support its use in both in vitro and in vivo studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies have evaluated LY3020371 HCl in animal models. As an mGlu2/3 antagonist, its toxicity profile is related to modulation of glutamatergic neurotransmission. No significant toxicity has been reported at therapeutic doses. The compound's safety profile supports its use in research applications.
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| References |
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| Additional Infomation |
LY3020371 HCl is a potent and selective mGlu2/3 receptor antagonist developed as a research tool for studying mGlu2/3 receptor function. Its mechanism involves blocking mGlu2/3 receptors, preventing the receptor-mediated inhibition of cAMP formation. The compound exerts antidepressant-like effects in vivo, making it a valuable tool for investigating the role of mGlu2/3 receptors in depression and other psychiatric disorders. LY3020371 HCl is primarily used for research purposes and has not received regulatory approval for clinical use.
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| Molecular Formula |
C15H16CLF2NO5S
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|---|---|
| Molecular Weight |
395.806049346924
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| Exact Mass |
395.04
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| CAS # |
1377615-44-5
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| Related CAS # |
LY3020371;1377615-75-2
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| PubChem CID |
69669746
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
552
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| Defined Atom Stereocenter Count |
6
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| SMILES |
Cl.S(C1C=CC(=C(C=1)F)F)C[C@@H]1[C@H]([C@H]2[C@H](C(=O)O)[C@H]2[C@@]1(C(=O)O)N)O
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| InChi Key |
XETSGLSGWGGOTN-JPWNOPPSSA-N
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| InChi Code |
InChI=1S/C15H15F2NO5S.ClH/c16-7-2-1-5(3-8(7)17)24-4-6-12(19)9-10(13(20)21)11(9)15(6,18)14(22)23;/h1-3,6,9-12,19H,4,18H2,(H,20,21)(H,22,23);1H/t6-,9+,10+,11+,12-,15+;/m1./s1
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| Chemical Name |
(1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride
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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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