| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
mGlu1 receptors (Ki = 19 nM)
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|---|---|
| ln Vitro |
Metabotropic glutamate receptor type 1 (mGluR1) is thought to play important roles in the neurotransmission and pathogenesis of several neurological disorders. Here, we describe the radioligand binding properties and pharmacological effects of a newly synthesized, high-affinity, selective, and noncompetitive mGluR1 antagonist, 6-amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-a]benzimidazole-2-carboxamide (YM-298198). YM-298198 inhibited glutamate-induced inositol phosphate production in mGluR1-NIH3T3 cells with an IC50 of 16 +/- 5.8 nM in a noncompetitive manner. Its radiolabeled form, [3H]YM-298198, bound to mGluR1-NIH3T3 cell membranes with a KD of 32 +/- 8.5 nM and a Bmax of 2297 +/- 291 fmol/mg protein. In ligand displacement experiments using rat cerebellum membrane, an existing noncompetitive mGluR1 antagonist 7-(hydroxyimino)cyclo-propa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) competitively displaced [3H]YM-298198 binding, although glutamate and other mGluR1 ligands acting on a glutamate site failed to inhibit [3H]YM-298198 binding, suggesting that YM-298198 binds to CPCCOEt (allosteric) binding sites but not to glutamate (agonist) binding sites. Specificity was demonstrated for mGluR1 over mGluR subtypes 2 to 7, ionotropic glutamate receptors, and other receptor, transporter, and ion channel targets. [1]
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| ln Vivo |
In in vivo experiments, orally administered YM-298198 showed a significant analgesic effect in streptozotocin-induced hyperalgesic mice at doses (30 mg/kg) that did not cause Rotarod performance impairment, indicating that it is also useful even for in vivo experiments. In conclusion, YM-298198 is a newly synthesized, high-affinity, selective, and noncompetitive antagonist of mGluR1 that will be a useful pharmacological tool due to its highly active properties in vitro and in vivo. Its radiolabeled form [3H]YM-298198 will also be a valuable tool for future investigation of the mGluR1. [1]
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| References |
[1]. Radioligand binding properties and pharmacological characterization of 6-amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-a]benzimidazole-2-carboxamide (YM-298198), a high-affinity, selective, and noncompetitive antagonist of metabotropic glutamate receptor type 1. J Pharmacol Exp Ther . 2005 Oct;315(1):163-9.
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| Additional Infomation |
7-Amino-N-cyclohexyl-N,1-dimethyl-2-thiazo[3,2-a]benzimidazole carboxamide belongs to the benzimidazole class of compounds.
Antagonistic activity in mGluR1-NIH cells. YM-298198 inhibited glutamate-induced IP generation with an IC50 of 16 ± 5.8 nM (n = 3; Fig. 2A), while CPCCOEt inhibited this generation with an IC50 of 6.3 ± 0.48 μM. YM-298198 had no effect on basal IP generation at concentrations up to 10 μM (data not shown). YM-298198 concentration-dependently reduced the maximal IP generation response induced by glutamate (Fig. 2, B and C). YM-298198 also increased the EC50 value of glutamate in a concentration-dependent manner, while... YM-298198 (IC50 of 16 ± 5.8 nM) showed almost the same or higher potency in inhibiting glutamate-induced IP generation as existing mGluR1 antagonists (such as CPC-COEt and R214127) (Lavreysen et al., 2003), indicating that YM-298198 is an effective mGluR1 antagonist. YM-298198 reduced the maximum response of glutamate even at low concentrations, while previously reported allosteric antagonists CPC-COEt, BAY36-7602 and R214127 only had this effect at high concentrations (Hermans et al., 1998;...[1]). |
| Molecular Formula |
C18H22N4OS
|
|---|---|
| Molecular Weight |
342.45848
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| Exact Mass |
342.151
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| Elemental Analysis |
C, 57.06; H, 6.12; Cl, 9.36; N, 14.79; O, 4.22; S, 8.46
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| CAS # |
748758-45-4
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| Related CAS # |
748758-45-4 (YM 298198);1216398-09-2 (HCl);
|
| PubChem CID |
9819432
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4.425
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
484
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(SC2=NC3=C(N12)C=C(C=C3)N)C(=O)N(C)C4CCCCC4
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| InChi Key |
KCBXOMYXOBVLED-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H22N4OS/c1-11-16(17(23)21(2)13-6-4-3-5-7-13)24-18-20-14-9-8-12(19)10-15(14)22(11)18/h8-10,13H,3-7,19H2,1-2H3
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| Chemical Name |
7-amino-N-cyclohexyl-N,1-dimethyl-[1,3]thiazolo[3,2-a]benzimidazole-2-carboxamide
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| Synonyms |
YM-298198; 748758-45-4; YM298198; 7-amino-N-cyclohexyl-N,1-dimethyl-[1,3]thiazolo[3,2-a]benzimidazole-2-carboxamide; [3H]YM298198; [3H]-YM298198; GTPL1389; GTPL5392;
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.9200 mL | 14.6002 mL | 29.2005 mL | |
| 5 mM | 0.5840 mL | 2.9200 mL | 5.8401 mL | |
| 10 mM | 0.2920 mL | 1.4600 mL | 2.9200 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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