| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
LY456236 HCl selectively targets the metabotropic glutamate receptor 1 (mGlu1) with an IC₅₀ of 143 nM for mGlu1 and >10 μM for mGlu5, demonstrating high selectivity. It acts as a non-competitive antagonist, blocking mGlu1-mediated phosphoinositide hydrolysis. Additionally, it inhibits EGFR with an IC₅₀ of 0.91 μM.
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| ln Vitro |
LY456236 (2 μM; 30 min) inhibits the proliferation of OCCM-30 induced by DHPG [2].
In vitro, LY456236 HCl shows potent and selective antagonism of the mGlu1 receptor with an IC₅₀ of 143 nM, while exhibiting minimal activity against mGlu5 (IC₅₀ >10 μM). It inhibits phosphoinositide hydrolysis with an IC₅₀ of 0.145 μM. The compound also inhibits EGFR with an IC₅₀ of 0.91 μM and reduces the growth of PC-9 cells in co-culture models. |
| ln Vivo |
In mice (3-100 mg/kg; ip; once) and body weight (10-60 mg/kg; oral; once), LY456236 exhibits anticonvulsant effects.
In vivo, LY456236 HCl reduces hyperalgesic behavior induced by formalin in both mouse and rat models with ED₅₀ values of 28 and 16.3 mg/kg, respectively. It is orally bioactive and can be administered via oral routes for preclinical efficacy studies in pain and neurological disorder models. |
| Enzyme Assay |
Non-cellular receptor binding assays for LY456236 HCl involve radioligand displacement using membrane preparations expressing the human mGlu1 receptor. Membranes are incubated with a radiolabeled mGlu1 ligand and varying concentrations of the test compound. Bound radioactivity is measured by filtration and scintillation counting, and IC₅₀ values are calculated from competition binding curves.
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| Cell Assay |
Cell proliferation analysis [2]
Cell Types: OCCM-30 Cell Tested Concentrations: 2 μM Incubation Duration: 30 minutes, then incubated with DHPG for 72 hrs (hours) Experimental Results: DHPG-stimulated OCCM-30 proliferation was diminished. In vitro cellular experiments include measuring mGlu1-mediated phosphoinositide hydrolysis inhibition. Cells expressing mGlu1 receptors are pre-labeled with [³H]myo-inositol, then stimulated with an agonist in the presence of varying concentrations of LY456236. Accumulated [³H]inositol phosphates are measured, and IC₅₀ values are calculated from dose-response curves. Cell viability and proliferation assays are also performed in cancer cell lines. |
| Animal Protocol |
Animal/Disease Models: DBA/2 mice and CD1 mice, epilepsy model [3]
Doses: 3-100 mg/kg Route of Administration: intraperitoneal (ip) injection, once Experimental Results: Prevention of audiogenic (tetanic syndrome) in DBA/2 mice Dose-related anticonvulsant effects on threshold shock-induced seizures, threshold shock-induced seizures in CD1 mice, and 6 Hz shock-induced seizures in CD1 mice. Animal/Disease Models: Amygdala-ignited SD (SD (Sprague-Dawley)) rat [3] Doses: 10, 30 and 60 mg/kg Route of Administration: po (po (oral gavage)) once Experimental Results: Behavioral and electrographic seizures produced dose-related seizures at threshold stimulus intensities reduce. Dose-related increase in stimulation intensity required to produce generalized epileptic seizures. In vivo animal studies include formalin-induced hyperalgesia models in mice and rats. Animals are administered LY456236 HCl orally at various doses, and pain responses are measured. ED₅₀ values are calculated to assess analgesic efficacy. The compound's effects on mGlu1-mediated behaviors and neurological function can also be evaluated in appropriate models. |
| ADME/Pharmacokinetics |
LY456236 HCl is orally bioavailable with favorable pharmacokinetic properties. It can be administered orally in preclinical studies. The compound has a molecular weight of 317.77 g/mol (C₁₆H₁₅N₃O₂·HCl). It is soluble in DMSO and is typically formulated for in vivo administration using standard vehicles.
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| Toxicity/Toxicokinetics |
Specific toxicity data for LY456236 HCl is limited in publicly available sources. As a selective mGlu1 receptor antagonist, it is expected to have on-target effects related to glutamatergic signaling modulation. Standard preclinical toxicology studies would be required for therapeutic development. The compound is for research use only and should be handled with appropriate safety precautions.
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| References |
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| Additional Infomation |
LY456236 HCl (also known as MPMQ hydrochloride) is a potent, selective, non-competitive, and orally active mGlu1 receptor antagonist with an IC₅₀ of 143 nM. It is a valuable research tool for studying mGlu1 receptor function in neurological disorders and pain. The compound is for research purposes only and is not for human therapeutic use.
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| Molecular Formula |
C16H15N3O2.HCL
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|---|---|
| Molecular Weight |
317.77014
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| Exact Mass |
317.093
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| Elemental Analysis |
C, 60.48; H, 5.08; Cl, 11.16; N, 13.22; O, 10.07
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| CAS # |
338736-46-2
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| Related CAS # |
338736-46-2 (HCl);338738-57-1;
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| PubChem CID |
9926998
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.265
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
22
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| Complexity |
321
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC=C(NC2=C3C=C(OC)C=CC3=NC=N2)C=C1.[H]Cl
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| InChi Key |
AVKFOWUSTVWZQN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H15N3O2.ClH/c1-20-12-5-3-11(4-6-12)19-16-14-9-13(21-2)7-8-15(14)17-10-18-16;/h3-10H,1-2H3,(H,17,18,19);1H
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| Chemical Name |
6-methoxy-N-(4-methoxyphenyl)quinazolin-4-amine;hydrochloride
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| Synonyms |
LY456236 HCl; LY456236 Hydrochloride; LY456236; LY 456236; LY-456236.
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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 (~786.73 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1469 mL | 15.7347 mL | 31.4693 mL | |
| 5 mM | 0.6294 mL | 3.1469 mL | 6.2939 mL | |
| 10 mM | 0.3147 mL | 1.5735 mL | 3.1469 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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