| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Skeletal muscle myosin-2 (fast skeletal myosin heavy chain isoforms).
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| ln Vitro |
In human muscle myosin samples, MPH-220 (0-50 µM) suppresses actin-activated ATPase activity [1].
MPH-220 selectively inhibits fast skeletal muscle myosin-2 activity, leading to direct muscle relaxation. At concentrations of 0-50 uM, the compound inhibits myosin ATPase activity and reduces force generation in isolated muscle fibers. It functions as a direct myosin inhibitor rather than affecting neuronal signaling, neuromuscular transmission, or calcium handling. Detailed IC50 values for myosin ATPase inhibition are not specified in standard datasets. |
| ln Vivo |
In anesthetized rats, MPH-220 (25–30 mg/kg, intraperitoneal injection or oral gavage) decreases skeletal muscle strength without having an impact on the cardiovascular system [1]. Brain-damaged rats' gait function is improved by MPH-220 (15 mg/kg, oral) [1].
MPH-220 is an orally active anti-spastic agent. In a rat model of brain injury-induced spasticity, MPH-220 (15 mg/kg, oral administration) significantly improves spastic gait function and reduces muscle stiffness. The compound has been evaluated in preclinical animal models and demonstrates efficacy as an anti-spastic drug candidate. It is described as a new-generation anti-spastic oral drug candidate with high potential for spasticity therapy. |
| Enzyme Assay |
Assay: In vitro myosin ATPase activity assay. Protocol: Purified fast skeletal muscle myosin-2 is incubated with varying concentrations of MPH-220 (0.1-50 uM) in ATPase reaction buffer containing ATP and KCl. After incubation at 25degC for 10-30 minutes, the amount of inorganic phosphate released is quantified using a malachite green or Biomol Green reagent. The IC50 for myosin ATPase inhibition is calculated as the concentration inhibiting 50% of ATPase activity.
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| Cell Assay |
Cells/Cells: Isolated skeletal muscle fibers or myotubes. Protocol: Primary skeletal muscle cells are differentiated into myotubes. Myotubes are treated with MPH-220 (0-50 uM) for 1-24 hours. Myosin ATPase activity can be measured in cell lysates. Alternatively, contractility of isolated single muscle fibers can be assessed using a force transducer; fibers are treated with MPH-220, and tetanic force production is measured. However, detailed cell-based assay protocols for myosin inhibitors are not widely standardized.
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| Animal Protocol |
Animal/Disease Models: Anesthetized rats[1]
Doses: 25-30 mg/kg Route of Administration: intraperitoneal (ip)injection or po (oral gavage) Experimental Results: diminished skeletal muscle force. Observed MPH-220 distribution in rat tissues in a time-dependent manner and a dose-dependent, few-fold accumulation in skeletal muscle. Animal Model: Rat model of spasticity (e.g., brain injury-induced spastic gait model). Protocol: Rats with induced brain injury and subsequent spasticity are administered MPH-220 orally (gavage) at 15 mg/kg. Gait function is assessed using a gait analysis system (e.g., CatWalk) measuring parameters such as stride length, swing speed, and paw placement. Muscle stiffness is measured by passive stretch resistance. Blood and brain tissue may be collected for PK and biodistribution analysis. |
| ADME/Pharmacokinetics |
MPH-220 is orally active with good bioavailability. It has been evaluated in animal models at 15 mg/kg oral dose, demonstrating in vivo efficacy for improving spastic gait. The compound is a selective inhibitor of fast skeletal muscle myosin-2, which likely contributes to its favorable safety profile by avoiding effects on cardiac muscle myosin (slow myosin) and smooth muscle myosin. Detailed PK parameters are not provided in standard datasets.
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| Toxicity/Toxicokinetics |
MPH-220 is reported to have no cardiovascular and neuronal side effects in preclinical studies. As a selective inhibitor of fast skeletal muscle myosin-2, it does not significantly inhibit cardiac (slow myosin-2) or smooth muscle myosin, minimizing off-target effects on heart and blood vessels. In animal models, the compound is well-tolerated at efficacious doses (e.g., 15 mg/kg oral). Comprehensive toxicological profiling is ongoing.
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| References | |
| Additional Infomation |
MPH-220 is a first-in-class oral anti-spastic drug candidate that directly inhibits fast skeletal muscle myosin-2. Its nervous system-independent mechanism provides high potential for spasticity therapy without the central side effects (sedation, cognitive impairment) of GABAergic drugs like baclofen or the cardiovascular side effects of botulinum toxin or systemic anesthetics. It is not FDA-approved and is in preclinical/early clinical research. MPH-220 enables muscle relaxation and is used in research of spasticity and muscle stiffness.
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| Molecular Formula |
C20H21N3O3S
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|---|---|
| Molecular Weight |
383.46404337883
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| Exact Mass |
383.13
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| CAS # |
2649776-79-2
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| PubChem CID |
155511990
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| Appearance |
Orange to red solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
27
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| Complexity |
630
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C12N(C3=CC=C(N4CCOCC4)C=C3)CC[C@@]1(O)C(=O)C1C=C(C)SC=1N=2
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| InChi Key |
KUIAFBSRBMWQQP-HXUWFJFHSA-N
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| InChi Code |
InChI=1S/C20H21N3O3S/c1-13-12-16-17(24)20(25)6-7-23(19(20)21-18(16)27-13)15-4-2-14(3-5-15)22-8-10-26-11-9-22/h2-5,12,25H,6-11H2,1H3/t20-/m1/s1
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| Chemical Name |
(9S)-9-hydroxy-5-methyl-12-(4-morpholin-4-ylphenyl)-4-thia-2,12-diazatricyclo[7.3.0.03,7]dodeca-1,3(7),5-trien-8-one
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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 | 2.6078 mL | 13.0392 mL | 26.0783 mL | |
| 5 mM | 0.5216 mL | 2.6078 mL | 5.2157 mL | |
| 10 mM | 0.2608 mL | 1.3039 mL | 2.6078 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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