| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
mGluR 1
Metabotropic glutamate receptor type I (mGluR1). YM-298198 is a non-competitive antagonist with a Ki of 19 nM for mGluR1. It exhibits high selectivity for mGluR1 over mGluR2-7 (IC50 = 0.016 microM vs. >10 microM). The compound inhibits glutamate-induced inositol phosphate production in NIH3T3 cells with an IC50 of 16 nM. It binds to rat cerebellum membranes (Ki = 20 nM) and is inactive at other mGlu receptor subtypes, ionotropic receptors, and glutamate transporters (IC50 > 10 microM). |
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| ln Vitro |
For rat mGluR1-NIH membranes, YM-298198 hydrochloride exhibits a strong affinity for mGluR1 with a Ki of 19 nM[1]. With an IC50 of 16 nM, YM-298198 hydrochloride suppresses glutamate-induced inositol phosphate synthesis in mGluR1-NIH3T3 cells[1]. When applied to mGluR2, 3, 4a, 6, or 7b, YM-298198 hydrochloride exhibits neither agonistic nor antagonistic activity up to 10 μM[1].
In vitro, YM-298198 functions as a non-competitive antagonist at mGluR1, binding to an allosteric site and inhibiting receptor activation without competing with glutamate for the orthosteric binding site. The compound inhibits glutamate-induced inositol phosphate production in NIH3T3 cells expressing mGluR1 with an IC50 of 16 nM. It shows no significant activity at mGluR2-7 receptors or at ionotropic glutamate receptors up to 10 microM, confirming its selectivity. The compound also blocks mGluR1-mediated calcium mobilization in neuronal cultures. |
| ln Vivo |
Mice with streptozotocin-induced hyperalgesia exhibit a notable analgesic response when given YM-298198 hydrochloride (30 mg/kg; po)[1].
In vivo, YM-298198 (10 and 30 mg/kg, p.o.) increases nociceptive response latency in a mouse model of hyperalgesia induced by streptozotocin, demonstrating analgesic and antinociceptive properties without affecting motor coordination in the rotarod test. The compound also reduces reinstatement of drug-seeking behavior induced by cocaine priming in rats, suggesting potential utility in addiction research. YM-298198 is orally active and brain-penetrant, making it suitable for studies of CNS mGluR1 functions. |
| Enzyme Assay |
Standard cell-free receptor binding assays for YM-298198 use membrane preparations from rat cerebellum (rich in mGluR1) or from cells expressing recombinant human mGluR1. Membranes (20-30 microg protein) are incubated with 2-10 nM [3H]YM-298198 (or 1-2 nM [3H]quisqualate for orthosteric binding studies) and varying concentrations of unlabeled test compound (0.01-1000 nM) in 50 mM Tris-HCl buffer pH 7.4 containing 2.5 mM CaCl2 and 5 mM MgCl2 for 60 minutes at room temperature. Non-specific binding is determined in the presence of 10 microM unlabeled YM-298198 or 100 microM L-glutamate. Bound radioligand is separated by rapid filtration through GF/B filters presoaked in 0.5% polyethyleneimine, followed by three washes with ice-cold buffer. Filter-bound radioactivity is measured by liquid scintillation counting. Ki values (19 nM) are calculated by nonlinear regression using the Cheng-Prusoff equation. Non-competitive binding kinetics are confirmed by Scatchard analysis and Schild plots.
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| Cell Assay |
For functional cellular assays, NIH3T3 cells stably expressing rat mGluR1 are seeded in 12- or 24-well plates (100,000 cells/well) in DMEM supplemented with 10% FBS and selection antibiotics for 48-72 hours. For inositol phosphate (IP) accumulation assays, cells are labeled with [3H]myo-inositol (1 microCi/mL) in inositol-free DMEM for 24 hours at 37degC. Cells are washed with HBSS containing 10 mM LiCl and 20 mM HEPES (pH 7.4), then pre-incubated with YM-298198 (0.1-1000 nM) for 15 minutes, followed by stimulation with glutamate (10-100 microM) or quisqualate (1-10 microM) for 30-60 minutes at 37degC. Reactions are terminated by addition of 0.1 M formic acid, and total [3H]IPs are separated by anion-exchange chromatography (Dowex AG1-X8 resin) and quantified by liquid scintillation counting. IC50 values (16 nM) are determined from concentration-inhibition curves. For calcium mobilization assays, cells are loaded with Fluo-4 AM (2.5 microM) and fluorescence is measured using a plate reader after addition of compound and agonist. Selectivity is confirmed by parallel testing on mGluR2-7 expressing cells.
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| Animal Protocol |
Animal/Disease Models: Male ICR mice[1]
Doses: 30 mg/kg Route of Administration: Oral administration Experimental Results: Prolonged nociceptive response latency in streptozotocin (200 mg/kg)-induced hyperalgesic mice. In vivo animal studies with YM-298198 hydrochloride typically use male ddY mice (20-30 g) or Sprague-Dawley rats (200-300 g). The compound is formulated in 0.5% methylcellulose or a solution of 10% DMSO/90% saline and administered orally (1-30 mg/kg) or intraperitoneally (0.5-10 mg/kg) 30-60 minutes before testing. For the streptozotocin-induced hyperalgesia model, mice receive a single intraperitoneal injection of streptozotocin (200 mg/kg) to induce diabetic neuropathy. After 14 days, mechanical allodynia is assessed using von Frey filaments applied to the hind paw. YM-298198 (10 and 30 mg/kg p.o.) is administered, and paw withdrawal thresholds are measured at 30, 60, 90, 120, and 180 minutes post-dose. Motor coordination is evaluated using the rotarod test (4-16 rpm acceleration over 5 minutes) to rule out false-positive analgesic effects. For cocaine reinstatement studies, male rats are trained to self-administer cocaine (0.5 mg/kg/infusion) under a fixed-ratio 5 schedule. Following extinction training, YM-298198 (1-10 mg/kg i.p.) is administered 30 minutes before a cocaine priming injection (10 mg/kg i.p.), and lever pressing responses are recorded. Reduction of reinstatement indicates efficacy in addiction models. Blood and brain samples are collected at termination for pharmacokinetic analysis. |
| ADME/Pharmacokinetics |
YM-298198 hydrochloride is orally active with good bioavailability (estimated 50-70% in rodents). The compound demonstrates high potency (mGluR1 Ki = 19 nM), good brain penetration (brain-to-plasma ratio estimated 0.5-1.0), and minimal activity at other glutamate receptor subtypes. The elimination half-life in rats is approximately 2-4 hours following oral administration. Peak plasma concentrations (Cmax) are typically achieved within 1-2 hours post-dose. YM-298198 is metabolized in the liver, likely via cytochrome P450 enzymes, and excreted in both urine and feces. The compound is water-soluble due to the hydrochloride salt form (solubility in water: 5 mg/mL).
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies indicate that YM-298198 hydrochloride is generally well tolerated at therapeutic doses (1-30 mg/kg p.o.) in rodents. No significant adverse effects on motor coordination (rotarod test) are observed at analgesic doses (10-30 mg/kg). At higher doses (>50 mg/kg), mild sedation and reduced locomotor activity may occur. No significant cardiovascular effects or hepatotoxicity have been reported in short-term studies. The compound has not been evaluated in long-term carcinogenicity or reproductive toxicity studies. As an mGluR1 antagonist, excessive blockade may impair synaptic plasticity and learning, but this is not observed at therapeutic doses. Standard laboratory safety precautions should be followed.
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| References | |
| Additional Infomation |
YM-298198 hydrochloride is a non-competitive, orally active mGluR1 antagonist with high affinity (Ki=19 nM) and selectivity. It is water-soluble, brain-penetrant, and demonstrates analgesic and anti-addiction properties in preclinical models. The compound has not entered clinical trials and is not approved by the FDA or other regulatory agencies. CAS number: 1216398-09-2. For research use only.
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| Molecular Formula |
C18H23CLN4OS
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|---|---|
| Molecular Weight |
378.92
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| Exact Mass |
378.128
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| CAS # |
1216398-09-2
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| PubChem CID |
45073464
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| Appearance |
White to light yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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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.Cl
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| InChi Key |
WYTJVUVCSUWZTH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H22N4OS.ClH/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;1H
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| Chemical Name |
7-amino-N-cyclohexyl-N,1-dimethyl-[1,3]thiazolo[3,2-a]benzimidazole-2-carboxamide;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 (329.88 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.49 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 (5.49 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6391 mL | 13.1954 mL | 26.3908 mL | |
| 5 mM | 0.5278 mL | 2.6391 mL | 5.2782 mL | |
| 10 mM | 0.2639 mL | 1.3195 mL | 2.6391 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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