| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
mGluR1a 8.8 μM (IC50)
Metabotropic glutamate receptor 1a (mGluR1a). |
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| ln Vitro |
Maximum reductions in NMDA toxicity range from 40% to 60%. LY367385 hydrochloride binds to N-methyl-D-aspartate (NMDA) during hazardous pulses, attenuating neuronal degeneration in a concentration-dependent way. LY367385 hydrochloride was more effective than LY367366, and none of these substances by itself had any effect on the vitality of neurons. At a dose of 10 nM, LY367385 hydrochloride demonstrated strong neuroprotection and a 50% reduction in the potentiating impact of (S)-3,5-dihydroxyphenylglycine (DHPG). Under experimental conditions involving greater antagonist doses, the amplifying impact of DHPG on NMDA toxicity was fully neutralized by LY367385 hydrochloride [2].
LY367385 hydrochloride inhibits quisqualate-induced phosphoinositide (PI) hydrolysis with an IC50 of 8.8 μM. It displays significantly higher selectivity for mGluR1a compared to mGluR5a, for which its IC50 is >100 μM. This selective inhibition of mGluR1a-mediated signaling pathways underscores its utility in dissecting mGluR1a-specific functions in vitro. |
| ln Vivo |
Intracerebroventricular (icv) administration of LY367385 hydrochloride has been used in DBA/2 mice and somnolescent mice (lh/lh), as well as central administration to the inferior colliculus of rats that are genetically prone to epilepsy (GEPR). LY367385 hydrochloride (ED50=12 nM, icv, 5 minutes) quickly and transiently inhibited sound-induced clonic seizures in DBA/2 mice. Following the treatment of LY367385 hydrochloride (250 nM) icv, the occurrence of spontaneous spikes and wave discharges on the electroencephalogram was dramatically reduced in sleepy mice [3]. This reduction occurred from 30 minutes to >150 minutes. Rats prone to hereditary epilepsy experience less clonic seizures when exposed to LY367385 hydrochloride. After two to four hours, LY367385 hydrochloride at 160 nM on both sides totally prevents clonic seizures [3].
The compound has been shown to inhibit the induction of long-term potentiation (LTP), a cellular correlate of learning and memory. Its neuroprotective and anticonvulsant effects have been observed in various in vivo models, suggesting its potential in mitigating excitotoxic neuronal damage and seizure activity. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays typically involve competition binding experiments using radiolabeled ligands specific to mGluR1a in membrane preparations from cells expressing the receptor. The ability of LY367385 hydrochloride to displace the radioligand is measured to determine its binding affinity (Ki). Functional antagonism is assessed by measuring its capacity to inhibit agonist-induced PI hydrolysis in these preparations.
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| Cell Assay |
Cells expressing recombinant mGluR1a (e.g., CHO or HEK-293 cells) are cultured and preloaded with [3H]-myo-inositol to label phosphoinositides. Cells are then stimulated with a receptor agonist (e.g., quisqualate or glutamate) in the presence or absence of varying concentrations of LY367385 hydrochloride. The accumulation of [3H]-inositol phosphates is measured to determine the compound's inhibitory effect on receptor-mediated PI hydrolysis.
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| Animal Protocol |
In standard rodent models, the compound is typically administered via intraperitoneal (i.p.) or intravenous (i.v.) injection. Anticonvulsant activity is evaluated in models such as maximal electroshock seizure (MES) or pentylenetetrazole (PTZ)-induced seizure tests. Neuroprotective effects are assessed in models of excitotoxicity, such as focal cerebral ischemia, by measuring infarct volume and neurological deficits following treatment.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data are publicly available for this specific compound. As a small molecule, its properties are expected to be consistent with those of typical research chemicals. For related mGluR antagonists, pharmacokinetic parameters such as half-life (t1/2), volume of distribution (Vd), and clearance (CL) are generally determined following intravenous and oral administration in rodent models.
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| Toxicity/Toxicokinetics |
Standard acute toxicity studies are typically conducted in rodents to determine the median lethal dose (LD50) or maximum tolerated dose (MTD). Observed side effects are generally related to its mechanism of action, potentially including CNS depression or motor impairment. Comprehensive toxicological profiles are not publicly disclosed for this research compound.
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| References |
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| Additional Infomation |
As a selective mGluR1a antagonist, LY367385 hydrochloride is primarily used as a research tool to investigate the role of mGluR1a in neurological disorders such as epilepsy, neurodegenerative diseases, and pain. It is not approved for human therapeutic use and is strictly for preclinical research purposes. Its high selectivity makes it a valuable compound for differentiating mGluR1a-mediated effects from those of other mGluR subtypes.
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| Molecular Formula |
C10H12CLNO4
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|---|---|
| Molecular Weight |
245.66
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| Exact Mass |
245.045
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| CAS # |
2829282-00-8
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| Related CAS # |
LY367385;198419-91-9
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| PubChem CID |
122360845
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
16
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| Complexity |
266
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| Defined Atom Stereocenter Count |
1
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| SMILES |
OC(C1C=CC([C@@H](C(=O)O)N)=C(C)C=1)=O.Cl
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| InChi Key |
IGKQWSUZDKTEPR-QRPNPIFTSA-N
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| InChi Code |
InChI=1S/C10H11NO4.ClH/c1-5-4-6(9(12)13)2-3-7(5)8(11)10(14)15;/h2-4,8H,11H2,1H3,(H,12,13)(H,14,15);1H/t8-;/m0./s1
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| Chemical Name |
4-[(S)-amino(carboxy)methyl]-3-methylbenzoic acid;hydrochloride
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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 (508.83 mM)
H2O: 12.5 mg/mL (50.88 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.47 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 (8.47 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 (8.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 50 mg/mL (203.53 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0707 mL | 20.3533 mL | 40.7067 mL | |
| 5 mM | 0.8141 mL | 4.0707 mL | 8.1413 mL | |
| 10 mM | 0.4071 mL | 2.0353 mL | 4.0707 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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