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Isosorbide di-(methyl fumarate)

Alias: IDMF
Cat No.:V138160 Purity: ≥98%
Isosorbide di-(methyl fumarate) is a topical DMF derivative that can activate the NRF2/ARE pathway.
Isosorbide di-(methyl fumarate)
Isosorbide di-(methyl fumarate) Chemical Structure CAS No.: 2013542-44-2
Product category: Keap1-Nrf2
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
Other Sizes
Official Supplier of:
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Product Description
Isosorbide di-(methyl fumarate) is a topical DMF derivative that activates the NRF2/ARE pathway. Isosorbide di-(methyl fumarate) downregulates ANCR target genes, regulates epithelial differentiation, and inhibits the expression of pro-inflammatory cytokine genes, IL-17A and TNF-induced keratinocyte genes, psoriatic lesion-specific genes, and immune response genes. Isosorbide di-(methyl fumarate) stimulates the transcription of oxidative stress response genes and reduces erythema and scaling in imiquimod-induced psoriatic lesions. Isosorbide di-(methyl fumarate) has no genotoxicity or radiosensitivity to dermal fibroblasts and is non-irritating and non-sensitizing in rodent models. Isosorbide di-(methyl fumarate) can be used in research on psoriasis vulgaris.
Biological Activity I Assay Protocols (From Reference)
ln Vitro
Dimethyl fumarate isosorbide difurate (25-100 μg/mL; 1 hour) has no phototoxicity to neonatal human dermal fibroblasts [1]. Dimethyl fumarate isosorbide difurate (1-200 μg/mL) has no mutagenic effect on Salmonella Typhimurium strains TA1535 and TA1537 [1]. In cytokine-stimulated human keratinocytes, dimethyl fumarate isosorbide difurate (24 hours) upregulates genes related to oxidative stress and exogenous metabolism, while downregulating genes related to immune response and epithelial differentiation [1]. Dimethyl fumarate isosorbide difurate (1-10 μg/mL; 24 hours) activates the NRF2/ARE pathway in human embryonic kidney 293 cells and significantly increases the expression of luciferase reporter genes [1].
ln Vivo
Applying dimethyl isosorbide (100 mg cream; topical; 5 days a week; for 13 days) to the tail skin of normal mice increased granular layer thickness and hyperkeratosis without causing skin irritation or pathological changes [1]. In female Wistar rats, dimethyl isosorbide (200–2000 mg/kg; topical; single dose) did not cause acute skin toxicity, skin irritation, or systemic adverse reactions [1]. In male New Zealand white rabbits, dimethyl isosorbide (500 mg; topical; single dose; 4 hours) caused only transient, mild skin irritation that subsided rapidly [1]. In Hartley guinea pigs, dimethyl isosorbide (100 mg; topical; 6 hours each time on days 0, 7, and 14 (induction); 6 hours each time on day 28 (challenge)) did not cause skin sensitization or systemic adverse reactions [1]. Isosorbide di(methyl fumarate) (5% emulsion; for external use; once daily for 6 days) significantly reduced erythema, scaling and skin thickness in imiquimod-induced psoriasis-like lesions in mice, while regulating gene expression to suppress immune response and promote epidermal development [1].
Cell Assay
Cytotoxicity assay [1]
Cell Types: Neonatal human dermal fibroblasts
Tested Concentrations: 25, 50, 100 μg/mL
Incubation Duration: 1 hour
Experimental Results: At a concentration of 25 μg/mL, the uptake rate of neutral red by UVA(-) cells was 97.1%, and that by UVA(+) cells was 84.7%. At a concentration of 50 μg/mL, the uptake rate of neutral red by UVA(-) cells was 57.5%, and that by UVA(+) cells was 53%. At a concentration of 100 μg/mL, the uptake rate of neutral red by UVA(-) cells was 1.3%, and that by UVA(+) cells was 0.3%. The results showed that UVA treatment significantly reduced cell viability at 0, 25, and 50 μg/mL, but the reduction in viability was similar for UVA(-) and UVA(+) cells at each concentration, indicating no phototoxic effect.
Animal Protocol
Animal/Disease Models:BALB/c (male, 5-7 weeks old) [1]
Doses: 100 mg IDMF topical cream
Route of Administration: Topical application; once daily (5 days a week); for 13 days
Experimental Results: No erythema or increased scaling was observed. Granular layer thickness increased by 28%, and hyperkeratosis increased by 34.5%. No leukocyte infiltration, parakeratosis, or hyperkeratosis was observed.
Animal/Disease Models:BALB/c (male, 8-9 weeks old, psoriasis-like lesions induced by daily topical application of 5% imiquimod cream for 5 consecutive days) [1]
Doses: 5% imiquimod cream
Route of Administration: Topical application; once daily; for 6 days (administered 1 hour after application of imiquimod cream on days 1-5, and administered alone on day 6)
Experimental Results: Skin erythema was significantly reduced on days 5 and 6. Skin scaling/desquamation and skin thickness were reduced on day 6. 68 genes related to hair growth cycle and epidermal development were upregulated. 98 genes related to immune response activation, granulocyte migration and immune effector processes were downregulated.
References

[1]. A Sensitization-Free Dimethyl Fumarate Prodrug, Isosorbide Di-(Methyl Fumarate), Provides a Topical Treatment Candidate for Psoriasis. JID Innov. 2021;1(4):100040. Published 2021 Jul 8.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C16H18O10
Molecular Weight
370.31
CAS #
2013542-44-2
Appearance
White to light yellow solid
SMILES
COC(/C=C/C(O[C@H]1[C@]2([H])[C@@](OC1)([H])[C@H](CO2)OC(/C=C/C(OC)=O)=O)=O)=O
Synonyms
IDMF
HS Tariff Code
2934.99.9001
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)
Solubility Data
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
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
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*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 : PEG300Tween 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).
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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL 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).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.7004 mL 13.5022 mL 27.0044 mL
5 mM 0.5401 mL 2.7004 mL 5.4009 mL
10 mM 0.2700 mL 1.3502 mL 2.7004 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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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