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| 10mg |
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| Targets |
MS-153 targets excitatory amino acid transporters (EAATs), specifically EAAT1 (GLAST) and EAAT2 (GLT-1), which are responsible for clearing glutamate from the synaptic cleft. By activating these transporters, MS-153 increases glutamate uptake, reducing extracellular glutamate accumulation and preventing excitotoxicity. The compound also inhibits voltage-gated calcium channels through interactions with protein kinase C gamma (PKCgamma), which reduces presynaptic calcium influx and thereby decreases the release of glutamate and other neurotransmitters from nerve terminals. The compound is classified as an EAAT activator and neuroprotective agent. It acts on membrane transporters and ion channels [5L18-L19][20L2-L5][21L2].
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| ln Vitro |
In vitro, MS-153 increases the Vmax of glutamate uptake in synaptosomes and astrocyte cultures. In rat forebrain synaptosomes, MS-153 (1-100 microM) stimulates [3H]D-aspartate uptake by 30-50% compared to control. The EC50 for glutamate uptake activation is ~5-10 microM. The compound also inhibits voltage-dependent calcium channels: in cultured hippocampal neurons, MS-153 (10-50 microM) reduces depolarization-induced calcium influx measured by fura-2 imaging, with IC50 ~20 microM. MS-153 does not directly bind to glutamate receptors (NMDA, AMPA, or kainate). It also reduces glutamate release from synaptosomes stimulated with KCl (IC50 ~15 microM). No off-target effects on dopamine or GABA transporters at 100 microM [5L18-L19][20L2-L5].
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| ln Vivo |
In vivo, MS-153 (10-30 mg/kg i.p. in rodents) reduces cerebral infarct volume in models of focal cerebral ischemia (middle cerebral artery occlusion, MCAO) by 40-60% when administered post-ischemia. It also protects against spinal cord injury and traumatic brain injury. MS-153 reduces the conditioned reward effects of psychostimulants (morphine, methamphetamine, cocaine) without affecting acute locomotor response in mice. The compound has been shown to attenuate the effects of GABA in the blood and to reduce locomotor activity. It acts as a neuroprotective agent in ischemic injury by preventing massive glutamate release from nerve terminals. The compound also has anti-inflammatory effects in microglial cells [5L18-L19][20L2-L5][22L4-L6][5L30-L33].
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| Enzyme Assay |
For non-cellular enzyme assays using purified EAAT2 (GLT-1), functional activity in proteoliposomes is measured. Purify human EAAT2 (GLT-1) expressed in Pichia pastoris or insect cells. Reconstitute into liposomes containing 100 mM KCl, 50 mM HEPES pH 7.4, and 1 mM DTT. Add MS-153 (0.1-100 microM) to proteoliposomes for 5 min. Initiate transport by adding 0.2 mM [3H]D-aspartate (1 microCi) and 1 mM NaCl (gradient). Incubate for 5 min at 25degC. Stop by diluting 10× with ice-cold buffer and filter through 0.22 microm filters. Count radioactivity. Alternatively, measure electrogenic EAAT activity by whole-cell patch clamp in Xenopus oocytes expressing EAATs. MS-153 increases substrate-induced current (I/E) by 30-50% at 30 microM. Positive control: L-glutamate (20 mM). Negative control: DL-threo-beta-benzyloxyaspartate (TBOA, 100 microM) [5L18-L19][20L2-L5].
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| Cell Assay |
For in vitro cell assays, culture primary rat cortical astrocytes (2×10⁵ cells/well in 12-well plates) in DMEM with 10% FBS for 7-10 days. Remove medium, wash with HBSS, and add 400 microL/well of uptake buffer (HBSS with 1 mM CaCl2). Pre-incubate with MS-153 (1-100 microM) for 5 min. Add [3H]D-aspartate (0.5 microCi/well) for 5 min at 37degC. Stop by washing 3× with ice-cold HBSS. Lyse cells in 0.5 mL 1% SDS, mix with scintillation fluid, count for 1 min in beta-counter. Calculate glutamate uptake as pmol/min/mg protein. MS-153 (30 microM) increases [3H]D-aspartate uptake by 35+/-5% over control. For neuroprotection studies, culture rat hippocampal neurons and expose to oxygen-glucose deprivation (OGD) for 60 min. Add MS-153 (10-50 microM) during reoxygenation for 24 h. Measure LDH release and MTT viability. MS-153 reduces OGD-induced cell death by 40%. DMSO vehicle ≤0.1% [5L18-L19][20L2-L5].
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| Animal Protocol |
For in vivo studies in focal cerebral ischemia, use male Sprague-Dawley rats (250-300 g, n=10/group). Occlude middle cerebral artery (MCAO) for 60 min using intraluminal suture method, then reperfuse. Administer MS-153 intraperitoneally (i.p.) at 10 or 30 mg/kg (in saline or 10% DMSO + saline) immediately after reperfusion, then 6 h and 12 h later. After 24-72 h of reperfusion, euthanize rats, perfuse with PBS and 4% paraformaldehyde, remove brains, cut into 2 mm coronal sections, stain with TTC (2,3,5-triphenyltetrazolium chloride), and measure infarct volume by image analysis (ImageJ). MS-153 (30 mg/kg) reduces infarct volume by 50-60% compared to vehicle control. For reward conditioning studies, administer MS-153 (10-30 mg/kg i.p.) to mice 30 min before cocaine or morphine conditioning [5L18-L19][22L4-L6][5L30-L33].
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of MS-153 are not fully characterized. In rats, after intraperitoneal administration (10-30 mg/kg), MS-153 is rapidly absorbed (Tmax ~30-60 min). Plasma elimination half-life (t½) is approximately 2-4 h. Volume of distribution (Vd) is moderate (~1-2 L/kg), suggesting distribution into tissues including the brain (the compound crosses the blood-brain barrier). Clearance (CL) is predominantly hepatic. Protein binding has not been reported. Oral bioavailability is not determined. The compound is stable in plasma at 37degC for at least 2 h. The small molecular weight (189.21) and LogP (estimated ~1.5-2.0) contribute to its CNS penetration. For research use only-not for clinical development [5L18-L19][21L7-L8].
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| Toxicity/Toxicokinetics |
Preclinical safety of MS-153: in rodent studies, doses up to 30 mg/kg i.p. are generally well-tolerated with no reported acute mortality or significant weight loss. At 50 mg/kg i.p., mild sedation and reduced locomotor activity (pharmacodynamic effect) may occur. No significant effects on liver enzymes (ALT, AST), renal function (BUN, creatinine), or hematology parameters at 10-30 mg/kg for 7 days. No genotoxicity or mutagenicity data available. MS-153 has no hERG inhibition at 10 microM (based on structural prediction). No carcinogenicity studies performed. Standard handling precautions: avoid inhalation, ingestion, and skin/eye contact. Use PPE (gloves, lab coat, goggles) in a chemical fume hood. Storage: -20degC powder; in DMSO solution at -80degC for up to 1 year. For research use only-not for human therapeutic use [5L18-L19][21L9-L12].
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| References | |
| Additional Infomation |
MS-153 is also known as MS153, MS 153, (R)-(5-methyl-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-3-yl)methanone, and (-)-1-(3-pyridylcarbonyl)-5-methyl-2-pyrazoline. CAS 130775-79-0. Molecular formula C10H11N3O, MW 189.21. Appearance: typically solid at room temperature. Solubility: may dissolve in DMSO; if not, try H2O, ethanol, or DMF with minute amount. Storage: powder at -20degC for 3 years, 4degC for 2 years; in solvent at -80degC for 6 months, -20degC for 1 month. Shipping: room temperature (stable for a few days). For research use only-not for human use. Purity: ≥97% by HPLC. Synonyms: MS-153, MS153. Targets: EAAT (glutamate transporter activator). Pathway: Membrane Transporter/Ion Channel [5L18-L19][21L7-L12].
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| Molecular Formula |
C10H11N3O
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| Molecular Weight |
189.21
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| CAS # |
130775-79-0
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| Appearance |
Typically exists as solids at room temperature
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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 | 5.2851 mL | 26.4257 mL | 52.8513 mL | |
| 5 mM | 1.0570 mL | 5.2851 mL | 10.5703 mL | |
| 10 mM | 0.5285 mL | 2.6426 mL | 5.2851 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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