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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Other Sizes |
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Ezutromid (also known as BMN-195 and SMTC-1100) is a first-in-class, orally bioavailable, small molecule modulator of the utrophin's translation with EC50 of 0.4 uM. It is currently in development to treat Duchenne muscular dystrophy (DMD) which is a lethal, progressive muscle wasting disease caused by a loss of sarcolemmal bound dystrophin, which results in the death of the muscle fibers leading to the gradual depletion of skeletal muscle. Ezutromid demonstrated significant disease modifying effects in DMD models and was safe and well tolerated with plasma concentrations achieved sufficient to cause a 50% increase in concentrations of utrophin in cells in vitro.
ln Vitro |
Increased utrophin RNA levels are induced in human muscle cells by ezutromid. After three days of treatment, utrophin protein levels in human DMD cells treated with Ezutromid increased twofold at an optimal concentration of 0.3 uM. Ezutromid was deemed safe and well-tolerated, as plasma concentrations were sufficiently high to result in a 50% rise in utrophin concentrations within cells. Ezutromid increased the level of Utrn mRNA by 30% and the level of UTRN protein by 2.0 times[3][4][5].
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ln Vivo |
Note: You can dissolve the products in 5% DMSO, 0.1% Tween-20, and phosphate buffered saline (PBS).
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Animal Protocol |
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References |
[1]. Chancellor DR, et al. Discovery of 2-arylbenzoxazoles as upregulators of utrophin production for the treatment of Duchenne muscular dystrophy. J Med Chem. 2011;54(9):3241-3250.
[2]. Chatzopoulou M, et al. Isolation, Structural Identification, Synthesis, and Pharmacological Profiling of 1,2-trans-Dihydro-1,2-diol Metabolites of the Utrophin Modulator Ezutromid. J Med Chem. 2020;63(5):2547-2556. [3]. Tinsley JM et al. Daily treatment with SMTC1100, a novel small molecule utrophin upregulator, dramatically reduces the dystrophic symptoms in the mdx mouse. PLoS One. 2011 May 6;6(5):e19189. [4]. Tinsley J et al. Safety, tolerability, and pharmacokinetics of SMT C1100, a 2-arylbenzoxazole utrophin modulator, following single- and multiple-dose administration to healthy male adult volunteers. J Clin Pharmacol. 2015 Jun;55(6):698-707. [5]. Guiraud S et al. Second-generation compound for the modulation of utrophin in the therapy of DMD. Hum Mol Genet. 2015 Aug 1;24(15):4212-24. |
Molecular Formula |
C19H15NO3S
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Molecular Weight |
337.39
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CAS # |
945531-77-1
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Related CAS # |
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SMILES |
O=S(C1=CC=C(OC(C2=CC=C3C=CC=CC3=C2)=N4)C4=C1)(CC)=O
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Synonyms |
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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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) |
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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 | 2.9639 mL | 14.8196 mL | 29.6393 mL | |
5 mM | 0.5928 mL | 2.9639 mL | 5.9279 mL | |
10 mM | 0.2964 mL | 1.4820 mL | 2.9639 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.
Effect of SMT C1100 onin vivoutrophin levels in themdxmouse.PLoS One.2011 May 6;6(5):e19189. th> |
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Ex vivoanalysis of SMT C1100 activity in themdxmouse.PLoS One.2011 May 6;6(5):e19189. td> |
Effect of SMT C1100 onin vivoparameters of exercisedmdxmice.PLoS One.2011 May 6;6(5):e19189. td> |
In vitroactivity of SMT C1100. th> |
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Effect of SMT C1100 treatment on calcium-dependent functional parameters of exercisedmdxmuscles.PLoS One.2011 May 6;6(5):e19189. td> |
Reduction in secondary pathological features. Plasma levels of SMT C1100 in the mouse. td> |