Synonym
LY456236 HCl; LY456236 Hydrochloride; LY456236 ; LY 456236 ; LY-456236.
IUPAC/Chemical Name
6-Methoxy-N-(4-methoxyphenyl)-4-quinazolinamine hydrochloride
InChi Key
AVKFOWUSTVWZQN-UHFFFAOYSA-N
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
SMILES Code
COC1=CC=C(NC2=C3C=C(OC)C=CC3=NC=N2)C=C1.[H]Cl
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
LY456236 HCl is a selective mGlu1 receptor antagonist (IC50 values are 143 nM and > 10 μM for mGlu1 and mGlu5 receptors respectively).
In vitro activity:
OCCM-30 cells, immortalized murine cementoblasts, were stimulated with l-glutamate or mGluRs antagonists. Dihydroxyphenylglycine (DHPG), an agonist of group I mGluRs (mGluR1 and mGluR5), also promoted cell proliferation, and this was inhibited by LY456236, an mGluR1 antagonist. DHPG increased the expression of cyclin D1, a key regulator of cell proliferation, and its nuclear translocation.
Reference: Connect Tissue Res. 2016 Sep;57(5):417-26. https://pubmed.ncbi.nlm.nih.gov/27261070/
In vivo activity:
The purpose of the present experiments was to characterize the anticonvulsant effects of the selective mGlu1 receptor antagonist LY456236 in mice and rats. In male and female DBA/2 mice, LY456236 produced a dose-related inhibition of sound-induced clonic-tonic seizures. In male CF1 mice, LY456236 produced a dose-related inhibition of tonic extensor seizures in the threshold electroshock model, and limbic seizures in the 6-Hz focal seizure model.
Reference: Neuropharmacology. 2005;49 Suppl 1:188-95. https://pubmed.ncbi.nlm.nih.gov/16011839/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
6.4 |
20.01 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
317.77
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Kanaya S, Komatsu H, Shimauchi H, Nemoto E. Metabotropic glutamate receptor 1 promotes cementoblast proliferation via MAP kinase signaling pathways. Connect Tissue Res. 2016 Sep;57(5):417-26. doi: 10.1080/03008207.2016.1195826. Epub 2016 Jun 3. PMID: 27261070.
2. Shannon HE, Peters SC, Kingston AE. Anticonvulsant effects of LY456236, a selective mGlu1 receptor antagonist. Neuropharmacology. 2005;49 Suppl 1:188-95. doi: 10.1016/j.neuropharm.2005.05.010. PMID: 16011839.
3. Barton ME, Shannon HE. Behavioral and convulsant effects of the (S) enantiomer of the group I metabotropic glutamate receptor agonist 3,5-DHPG in mice. Neuropharmacology. 2005 May;48(6):779-87. doi: 10.1016/j.neuropharm.2005.01.017. PMID: 15829250.
In vitro protocol:
1. Kanaya S, Komatsu H, Shimauchi H, Nemoto E. Metabotropic glutamate receptor 1 promotes cementoblast proliferation via MAP kinase signaling pathways. Connect Tissue Res. 2016 Sep;57(5):417-26. doi: 10.1080/03008207.2016.1195826. Epub 2016 Jun 3. PMID: 27261070.
In vivo protocol:
1. Shannon HE, Peters SC, Kingston AE. Anticonvulsant effects of LY456236, a selective mGlu1 receptor antagonist. Neuropharmacology. 2005;49 Suppl 1:188-95. doi: 10.1016/j.neuropharm.2005.05.010. PMID: 16011839.
2. Barton ME, Shannon HE. Behavioral and convulsant effects of the (S) enantiomer of the group I metabotropic glutamate receptor agonist 3,5-DHPG in mice. Neuropharmacology. 2005 May;48(6):779-87. doi: 10.1016/j.neuropharm.2005.01.017. PMID: 15829250.
1: Kanaya S, Komatsu H, Shimauchi H, Nemoto E. Metabotropic glutamate receptor 1 promotes cementoblast proliferation via MAP kinase signaling pathways. Connect Tissue Res. 2016 Sep;57(5):417-26. doi: 10.1080/03008207.2016.1195826. PubMed PMID: 27261070.
2: Rorick-Kehn LM, Hart JC, McKinzie DL. Pharmacological characterization of stress-induced hyperthermia in DBA/2 mice using metabotropic and ionotropic glutamate receptor ligands. Psychopharmacology (Berl). 2005 Dec;183(2):226-40. PubMed PMID: 16175401.
3: Shannon HE, Peters SC, Kingston AE. Anticonvulsant effects of LY456236, a selective mGlu1 receptor antagonist. Neuropharmacology. 2005;49 Suppl 1:188-95. PubMed PMID: 16011839.
4: Barton ME, Shannon HE. Behavioral and convulsant effects of the (S) enantiomer of the group I metabotropic glutamate receptor agonist 3,5-DHPG in mice. Neuropharmacology. 2005 May;48(6):779-87. PubMed PMID: 15829250.
5: Varty GB, Grilli M, Forlani A, Fredduzzi S, Grzelak ME, Guthrie DH, Hodgson RA, Lu SX, Nicolussi E, Pond AJ, Parker EM, Hunter JC, Higgins GA, Reggiani A, Bertorelli R. The antinociceptive and anxiolytic-like effects of the metabotropic glutamate receptor 5 (mGluR5) antagonists, MPEP and MTEP, and the mGluR1 antagonist, LY456236, in rodents: a comparison of efficacy and side-effect profiles. Psychopharmacology (Berl). 2005 Apr;179(1):207-17. PubMed PMID: 15682298.
6: Barton ME, Peters SC, Shannon HE. Comparison of the effect of glutamate receptor modulators in the 6 Hz and maximal electroshock seizure models. Epilepsy Res. 2003 Sep;56(1):17-26. PubMed PMID: 14529950.
