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Product name: Itaconic acid
Synonym name: Methylenebutanedioic acid；Propylenedicarboxylic acid
Catalogue No.: BP4247
Cas No.: 97-65-4
Formula: C5H6O4
Mol Weight: 130.099
Botanical Source:
Type of Compound:
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.
The product could be supplied from milligrams to grams
Inquire for bulk scale.
For Reference Standard and R&D, Not for Human Use Directly.
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
74.6000
-.2559
-2.2659
65.7040
1.4817
2.6724
Low
50.3581
2.5503
Yes
No
No
No
No
No
0.0
Yes
Yes
Yes
Yes
Itaconic acid (CAS number: 97-65-4), as an important dicarboxylic acid natural product, has attracted widespread attention in pharmacology and biomedical fields in recent years. Its unique chemical structure and biosynthetic pathway make it a junction between fungal and human metabolites, embodying the dual identity of natural and endogenous metabolites. Itconic acid is not only widely used as an important bio-based chemical in industrial biotechnology, but also, due to its potential roles in immune regulation, anti-inflammation, and metabolic reprogramming, has become a hot topic in natural product pharmacology research. Especially in the treatment of severe inflammatory diseases such as sepsis and inflammatory storms, itaconic acid demonstrates significant pharmacological activity by regulating multiple key molecular signaling pathways, indicating promising clinical application prospects.
This paper systematically reviews the chemical structure and physicochemical properties of itaconic acid, its plant origin and extraction methods, pharmacological activity, and its mechanism of action. It focuses on analyzing its molecular target regulatory role in sepsis and inflammatory storms, and, combined with druggability parameters, explores its pharmacokinetic characteristics and clinical application prospects, aiming to provide researchers in the field of natural product pharmacology with comprehensive and in-depth reference.
Itconic acid is a dicarboxylic acid, chemically named 2-methylenepropane dicarboxylic acid, with the molecular formula C5H6O4 and a molecular weight of 130.0990. Its structural feature is that one methyl hydrogen in the methacrylic acid framework is replaced by a carboxylic acid group, forming a fatty acid derivative containing two carboxyl groups. The molecular structure of itaconic acid contains an unsaturated alzene bond, which gives it certain reactivity and biofunctional diversity. Its structure is similar to succinic acid, both belonging to the dicarboxylic acid class, but the alken bonds of itaconic acid give it unique metabolic pathways and biological activity.
In terms of physicochemical properties, itaconic acid has a LogP value of -0.2559, indicating good hydrophilicity, with water solubility of 65.7040 mg/mL, indicating high solubility in the aqueous phase, facilitating absorption and distribution in the body. Its polar surface area (TPSA) is 74.6 Ų, indicating moderate molecular polarity and favorable binding to biomacromolecules. Low blood-brain barrier permeability means its distribution in the central nervous system is limited, which may reduce the risk of central toxicity. The hERG channel inhibition test was negative, indicating itconic acid is not likely to cause cardiotoxicity, while the Ames mutagenic test was 0.0, indicating low genotoxicity risk and a solid safety foundation.
Isconic acid was first discovered in fungal microorganisms, especially fungi of Aspergillus and Ustilago. Although itaconic acid itself is not a typical plant secondary metabolite, its presence in plant microbial symbiotic systems and the diversity of its metabolites make it a research hotspot. Naturally derived itaconic acid is mainly produced through microbial fermentation, which converts carbon sources into itaconic acid through fungal metabolic pathways.
Traditional isconic acid extraction relies on microbial fermentation, with commonly used carbon sources including glucose, glycerol, and starch. Fermentation conditions such as pH, temperature, aeration rate, and nutrient concentration all significantly affect itaconic acid yield. In recent years, advances in genetic engineering have made it possible to optimize itaconic acid synthesis pathways through gene editing, significantly improving yield and purity. In addition, the application of downstream purification technologies such as membrane separation, crystallization, and ion exchange has improved the industrial extraction efficiency of itaconic acid.
Although itaconic acid mainly originates from microbial fermentation, some studies have explored its biosynthetic potential in plant tissue cultures and symbiotic microbial systems, providing a theoretical basis for future diversified production.
Research on the pharmacological activity of itaconic acid has mainly focused on its anti-inflammatory, immunomodulatory, and metabolic reprogramming functions. As an endogenous metabolite, itaconic acid plays an important role in immune cell metabolism, especially prominently during the metabolic reprogramming of macrophages.
Anti-inflammatory effects
Itconic acid reduces inflammatory responses by inhibiting the production and release of inflammatory mediators. Research shows that itaconic acid can significantly reduce the expression of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6, inhibiting activation of inflammatory signaling pathways. Its anti-inflammatory effects have been validated in various inflammation models, including sepsis, mouse inflammatory bowel disease models, and lung injury models.
Immunomodulatory function
Itconic acid regulates the metabolic state of immune cells, promotes the transformation of macrophages from pro-inflammatory M1 type to anti-inflammatory M2 type, and regulates immune microenvironment balance. Additionally, itaconic acid affects the energy metabolism and functional status of immune cells by regulating the activity of immune-related enzymes.
Antioxidant and cell protection
Itconic acid can activate antioxidant responses and reduce cellular damage mediated by oxidative stress. By regulating the KEAP1-NRF2 signaling pathway, it enhances cellular antioxidant defenses and protects tissues from oxidative damage.
Metabolic regulation
As a metabolic intermediate, itaconic acid participates in the tricarboxylic acid cycle (TCA) bypass metabolism, regulating cellular energy metabolism and metabolic homeostasis. It plays a key role in regulating cellular metabolic reprogramming, influencing cell proliferation, differentiation, and function.
The pharmacological effects of itaconic acid depend on its regulation of multiple key molecular signaling pathways, especially prominent in pathological conditions such as sepsis and inflammatory storms. The main targets include:
NLRP3 inflammasome
NLRP3 inflammasomes are key regulators of inflammatory responses and are involved in the production of pro-inflammatory cytokines. Itconic acid inhibits the assembly and activation of NLRP3 inflammasomes, reduces the release of pro-inflammatory factors such as IL-1β, alleviates excessive inflammatory responses, and prevents inflammatory storms.
HIF-1α (hypoxia-inducible factor-1α)
HIF-1α plays a central role in inflammation and metabolic regulation. Itconic acid can regulate the stability and transcriptional activity of HIF-1α, influence metabolic reprogramming of inflammatory cells, inhibit the expression of pro-inflammatory genes, and promote anti-inflammatory responses.
KEAP1-NRF2 signaling pathway
KEAP1 acts as an inhibitory protein of NRF2, regulating cellular antioxidant responses. Itconic acid binds to KEAP1, releasing NRF2, activating antioxidant gene expression, enhancing cells' resistance to oxidative stress, and reducing tissue damage.
NF-κB signaling pathway
NF-κB is a core transcription factor in inflammatory responses, regulating the expression of various inflammatory genes. Itconic acid reduces pro-inflammatory cytokine expression by inhibiting NF-κB activation, thereby suppressing inflammatory cascade reactions.
ACOD1 (immune-related decarboxylase 1)
ACOD1 catalyzes the biosynthesis of itaconic acid and is a key enzyme in immune metabolism regulation. As a product of ACOD1, itaconic acid participates in feedback regulation, affecting immune cell metabolism and function, and modulating the intensity and duration of immune responses.
In summary, itaconic acid regulates inflammation and immune responses through multi-target and multi-pathway synergistic effects, demonstrating a complex and refined pharmacological regulatory network.
The druggability evaluation of itaconic acid shows it has promising potential for drug development:
Pharmacokinetics, itaconic acid, as a small-molecule metabolite, is metabolically stable in the body and is mainly excreted by the kidneys. Its hydrophilic and polar characteristics make it widely distributed in plasma, but its tissue permeability is limited. Due to low blood-brain barrier permeability, itaconic acid is less exposed to the central nervous system. Currently, detailed pharmacokinetic data on itaconic acid are insufficient; systematic in vivo metabolic kinetics and pharmacodynamic studies are needed in the future to optimize dosing regimens and formulation design.
Due to its unique immunomodulatory and anti-inflammatory effects, itaconic acid shows broad application prospects in clinical emergencies such as sepsis and inflammatory storms. Sepsis is a globally deadly inflammatory disease lacking effective targeted therapies. Itconic acid regulates inflammatory responses through multiple targets, offering new approaches for sepsis treatment.
In addition, itaconic acid is gradually being recognized for its potential applications in autoimmune diseases, metabolic syndrome, and chronic inflammatory diseases. Its ability to regulate immune metabolism makes it a candidate drug for treating diseases related to immune-metabolic disorders.
Future research should focus on:
With advances in biotechnology and drug development, itaconic acid is expected to become a major breakthrough in the field of natural product pharmacology, bringing new hope for the treatment of inflammatory diseases.
As a natural product with a unique structure and multiple biological functions, itaconic acid combines the dual advantages of metabolic regulation and immune regulation, demonstrating broad pharmacological activity and good druggability. Its multi-target mechanism of action in severe inflammatory diseases such as sepsis and inflammatory storms provides a solid foundation for the development of novel anti-inflammatory immunomodulatory drugs. Although current research on itaconic acid is still in its early stages, with advances in molecular pharmacology, metabolomics, and clinical translational studies, itaconic acid is expected to become an important direction for future natural product drug development. Systematic pharmacokinetics and preclinical research will lay the foundation for its clinical application, driving its advancement toward clinical translation and benefiting more patients.
Shenshuai
Wenjing
Hedandan
