| Size | Price | |
|---|---|---|
| Other Sizes |
| Targets |
Biochemical reagent
|
|---|---|
| ln Vitro |
The results showed that Dimethyl itaconate (DMI) suppressed astrocytes cell death induced by LPS in a dose-dependent manner. DMI dose-dependently restored the reduced mRNA and protein levels of NGF, BDNF, GDNF, and TrkA and TrkB receptors in LPS-treated astrocytes, but it significantly decreased the p75 expression in the same condition.
Conclusion: In conclusion, DMI may be able to support astrocyte survival and functions based on the restoration of neurotrophic factors and their receptors expression in LPS-stimulated astrocyte cells. This suggests that DMI could be a promising therapeutic option for neurodegenerative diseases characterized by inflammation-induced astrocyte dysfunction [2].
|
| ln Vivo |
Polycystic ovary syndrome (PCOS) is the most common cause of anovulation and infertility in women. Inflammation and oxidative stress are considered to be the causes of ovarian dysfunction in PCOS. Dimethyl itaconate, as a macrophage-derived immunometabolite, has anti-inflammatory and antioxidative properties, but limited data are available about its effect on female reproductive dysfunctions. The present study aimed to determine the effects of dimethyl itaconate, a cell-permeable derivative of itaconate, on the histological changes, oxidative stress, and inflammation in the ovaries of PCOS rats. In this experimental study, 48 mature female Wistar rats (160-180 g) were randomly divided into the six groups including control, PCOS, PCOS+Dimethyl itaconate (DMI), PCOS+ metformin, control Dimethyl itaconate (DMI)and control metformin. Following PCOS induction by using testosterone enanthate (1 mg/100 g/day for 35 days), the animals were treated with Dimethyl itaconate (DMI) (50 mg/kg) or metformin (300 mg/kg) for 30 days. At the end of the experimental period, the insulin resistance markers (serum insulin and glucose concentrations, and the homeostasis model assessment of basal insulin resistance (HOMA-IR), oxidative stress index (OSI), and inflammatory cytokines were measured. The process of Folliculogenesis was evaluated by histological examination of the ovary. The results showed that DMI improved insulin resistance and decreased TNF- and IL-1β levels and OSI in the ovarian tissue of rats following androgen-induced PCOS. It also improved steroidogenesis and Folliculogenesis by reducing cystic follicles and ovarian tissue structure. Results indicated that DMI may be a potential candidate to ameliorate PCOS adverse effects by reducing insulin resistance, inflammation, and oxidative stress and restoring ovarian Folliculogenesis [1].
|
| Cell Assay |
Primary rat astrocyte cells were isolated from one-day-old Wistar rats and exposed to 1 µg/ml lipopolysaccharide (LPS) for 6 h to stimulate inflammation. The effect of Dimethyl itaconate (DMI) (62.5, 125, and 250 µM for 18 h) on the cell viability of astrocyte cells exposed to LPS was evaluated by the MTT assay. The effects of DMI on the mRNA and protein levels of NGF, BDNF, and GDNF were evaluated using ELISA and qRT-PCR assays. Protein and mRNA levels of neurotrophic factor receptors (TrkA, TrkB, and P75) were evaluated using qRT-PCR and Western blot analyses [2].
|
| References |
[1]. Dimethyl itaconate mitigates histological distortions, inflammation, and oxidative stress in the rat model of polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2024 Oct:243:106546.
[2]. Dimethyl itaconate modulates neuroprotective effect on primary rat astrocytes under inflammatory condition by regulating the expression of neurotrophic factors and TrkA/B-P75 receptors. Neurol Res. 2024 Dec;46(12):1137-1148. |
| Additional Infomation |
Astrocytes, specialized glial cells, are essential for maintaining the central nervous system homeostasis. Inflammatory conditions can disrupt neurotrophic factors and receptor expression in astrocytes, leading to potential central nervous system damage. Itaconate, recently identified for its anti-inflammatory properties, was investigated in this study for its effects on neurotrophic factors in LPS-stimulated primary rat astrocytes.[2]
The metabolite itaconate has emerged as an important immunoregulator with roles in antibacterial defence, inhibition of inflammation and, more recently, as an inhibitory factor in obesity. Itaconate is one of the most upregulated metabolites in inflammatory macrophages. It is produced owing to the disturbance of the tricarboxylic acid cycle and the diversion of aconitate to itaconate via the enzyme aconitate decarboxylase 1. In immunology, initial studies concentrated on the role of itaconate in inflammatory macrophages where it was shown to be inhibitory, but this has expanded as the impact of itaconate on other cell types is starting to emerge. This review focuses on itaconate as a key immunoregulatory metabolite and describes its diverse mechanisms of action and its many impacts on the immune and inflammatory responses and in cancer. We also examine the clinical relevance of this immunometabolite and its therapeutic potential for immune and inflammatory diseases.Nat Metab. 2024 Sep;6(9):1661-1667. |
| Molecular Formula |
C7H10O4
|
|---|---|
| Molecular Weight |
158.15
|
| Exact Mass |
158.057
|
| CAS # |
617-52-7
|
| Related CAS # |
25587-85-3
|
| PubChem CID |
69240
|
| Appearance |
Colorless to off-white <37°C powder,>41°C liquid
|
| Density |
1.1±0.1 g/cm3
|
| Boiling Point |
208.0±0.0 °C at 760 mmHg
|
| Melting Point |
37-41 °C(lit.)
|
| Flash Point |
99.4±0.0 °C
|
| Vapour Pressure |
0.2±0.4 mmHg at 25°C
|
| Index of Refraction |
1.429
|
| LogP |
1.36
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
11
|
| Complexity |
183
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O(C([H])([H])[H])C(C([H])([H])C(=C([H])[H])C(=O)OC([H])([H])[H])=O
|
| InChi Key |
ZWWQRMFIZFPUAA-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C7H10O4/c1-5(7(9)11-3)4-6(8)10-2/h1,4H2,2-3H3
|
| Chemical Name |
dimethyl 2-methylidenebutanedioate
|
| Synonyms |
Dimethyl itaconate; 617-52-7; Dimethyl 2-methylenesuccinate; Dimethylitaconate; dimethyl 2-methylidenebutanedioate; Itaconic acid dimethyl ester; 1,4-dimethyl 2-methylidenebutanedioate; Butanedioic acid, methylene-, dimethyl ester;
|
| 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 (In Vitro) |
DMSO: 100 mg/mL (632.31 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (15.81 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 25.0 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: ≥ 2.5 mg/mL (15.81 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 25.0 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (15.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.3231 mL | 31.6156 mL | 63.2311 mL | |
| 5 mM | 1.2646 mL | 6.3231 mL | 12.6462 mL | |
| 10 mM | 0.6323 mL | 3.1616 mL | 6.3231 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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