Product name: (9Z,11E)-13-Oxo-9,11-octadecadienoic Acid
Synonym name: (9Z,11E)-13-Oxooctadeca-9,11-dienoic acid;13-KODE; 13-Oxo-9Z,11E-octadecadienoic acid; 13-Oxo-ODE; 13-OxoODE
Catalogue No.: BP2240
Cas No.: 54739-30-9
Formula: C18H30O3
Mol Weight: 294.435
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℃
54.3700
4.6985
2.2259
.0083
2.7906
2.8744
High
95.5829
2.3989
Yes
Yes
No
No
No
No
0.0
No
Yes
Yes
Yes
Natural products, as an important source of drug discovery, have long played an irreplaceable role in maintaining human health and treating diseases. Among the numerous biologically active natural lipid molecules, oxidized fatty acids and their metabolites have attracted much attention due to their key roles in cell signaling, inflammation regulation, and metabolic regulation. (9Z, 11E) -13-oxo-9,11-octadecadienoic acid ((9Z, 11E) -13-Oxo-9,11-octadecadienoic acid, abbreviated as 13-oxo-9Z, 11E-ODE) is an oxooctadecadienoic acid with a unique conjugated diene structure, belonging to an important member of the oxidized fatty acid family. This compound was initially isolated and identified from safflower (Carthamus tinctorius L.), and subsequently discovered in various plant and mammalian tissues, gradually revealing its biological function.
13-oxo-9Z, 11E-ODE is closely related in structure to 13-hydroxy-9Z, 11E-octadecadienoic acid (13-HODE), which is one of the main products of linoleic acid oxidation via the lipoxygenase pathway. 13-oxo-9Z, 11E-ODE, as the oxidation products of 13-MODE, show unique pharmacological activities in vivo and in vitro, especially in the regulation of cardiovascular diseases such as atherosclerosis, showing potential application value. In recent years, with the deepening understanding of the role of lipid metabolism and oxidative stress in the occurrence and development of diseases, significant progress has been made in pharmacological research on 13-oxo-9Z and 11E-ODE. The study of their mechanisms of action, molecular targets, and drug efficacy evaluation provides important basis for the development of new therapeutic strategies.
This article will systematically review the research progress of 13-oxo-9Z, 11E-ODE from the aspects of chemical structure and physicochemical properties, plant sources and extraction methods, pharmacological activity research, mechanism of action and molecular targets, drug evaluation and pharmacokinetics, clinical application prospects and prospects, in order to provide reference for the in-depth research and development of this natural product.
The chemical structure of 13-oxo-9Z, 11E-ODE consists of an 18 carbon chain containing a conjugated diene system and a ketone functional group. Specifically, its molecular structural features include: the carbon chain skeleton is octadecadienoic acid, with conjugated double bonds between positions 9 and 11, where the 9-position double bond is in the cis configuration (Z) and the 11 position double bond is in the trans configuration (E), forming a typical 9Z, 11E conjugated diene structure; There is a ketone group (=O) attached to the 13th carbon atom, hence it is named 13-oxo-9Z, 11E-octadecadienoic acid. The molecular formula of this compound is C18H30O3, with a molecular weight of 294.4350 g/mol.
From a stereochemical perspective, the 9Z, 11E conjugated diene structure endows the molecule with a specific spatial conformation, which is crucial for its interaction with biological targets. The conjugated dienone structural unit (- CH=CH-CH=CH-C (=O) -) is an important pharmacophore that participates in various biochemical reactions, including Michael addition reactions, redox reactions, and covalent modifications with proteins. It is worth noting that the structural difference between 13-oxo-9Z, 11E-ODE, and 13-HODE lies only in the difference of the functional group at position 13 (ketone group vs hydroxyl group), which leads to completely different biological activities and metabolic fates.
According to computational chemistry and experimental measurement data, 13-oxo-9Z and 11E-ODE exhibit the following key physicochemical properties:
fat-soluble The lipid water partition coefficient (LogP) of this compound is 4.6985, indicating its strong lipid solubility and tendency to distribute in lipid environments. This characteristic is consistent with its structural features as a derivative of long-chain fatty acids, and suggests that it may primarily interact with lipoproteins, cell membranes, or lipid binding proteins in vivo.
Polar Surface Area The topological polar surface area (TPSA) is 54.3700 Å ², which is at a moderate level, indicating that the molecule has certain polar regions (mainly from carboxyl and ketone groups), but overall it is still predominantly hydrophobic. The TPSA value is also commonly used to predict oral absorption and blood-brain barrier penetration ability, and the TPSA value of this compound suggests that it may have good membrane permeability.
Water solubility The water solubility is extremely low, only 0.0083 mg/mL, which is consistent with its high LogP value. Low water solubility is a common characteristic of long-chain fatty acid compounds and an important factor affecting their formulation development and bioavailability.
Blood-brain barrier penetration The prediction shows that the compound has high blood-brain barrier penetration ability, which is worth paying attention to because it may exert pharmacological effects in the central nervous system, while also posing potential neurotoxic risks.
Security prediction HERG inhibition prediction is negative, indicating a low risk of the compound causing QT interval prolongation in the heart; The Ames test result is 0.0, indicating that it may not have significant mutagenicity. These preliminary safety evaluation data provide favorable conditions for its further development.
13-oxo-9Z, 11E-ODE was initially isolated and identified from Carthamus tinctorius L., an annual herbaceous plant of the Asteraceae family. Its dried tubular flowers are a traditional Chinese medicinal herb with the effects of promoting blood circulation and meridian circulation, dispersing blood stasis and relieving pain. Red flowers are rich in various fatty acids and their oxidized derivatives, among which 13-oxo-9Z and 11E-ODE are important active ingredients. In addition to safflower, this compound has also been found in other plants, including certain leguminous and gramineous plants, but the content is usually low.
In plants, 13-oxo-9Z and 11E-ODE are believed to be products of linoleic acid oxidation metabolism, possibly generated through the lipoxygenase pathway or non enzymatic oxidation reactions. 13-oxo-9Z and 11E-ODE in plants may be involved in physiological processes such as defense responses, signal transduction, and growth and development regulation. It is worth noting that this compound has also been found as an endogenous metabolite in mammals, indicating its conserved biological function in evolution.
For the extraction of 13-oxo-9Z and 11E-ODE, the main method currently used is organic solvent extraction combined with chromatographic separation. Due to the lipophilic nature of the compound, commonly used extraction solvents include n-hexane, ether, ethyl acetate, chloroform methanol mixed solvents, etc. The extraction process usually includes the following steps:
Raw material pretreatment Dry plant materials (such as safflower) are crushed and soaked or refluxed with appropriate solvents for extraction. To improve extraction efficiency, ultrasound assisted extraction or microwave-assisted extraction techniques are often used.
Preparation of crude extract The crude extract is obtained by vacuum concentration of the extract, which contains a large amount of fatty acids, glycerides, and other fat soluble components.
Liquid-liquid distribution The crude extract is suspended in the aqueous phase and subjected to fractional extraction with organic solvents of different polarities to enrich the target compound. 13-oxo-9Z and 11E-ODE are mainly enriched in the extraction portion of medium polarity solvents (such as ethyl acetate).
chromatographic separation Further purification is carried out using silica gel column chromatography, preparative thin-layer chromatography, or high-performance liquid chromatography (HPLC). The commonly used mobile phase systems include gradient elution systems such as n-hexane ethyl acetate and n-hexane isopropanol. Reverse phase C18 chromatography columns are also commonly used for the separation and purification of this compound.
Structural Identification The purified compound was structurally confirmed by techniques such as nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS), infrared spectroscopy (IR), and ultraviolet spectroscopy (UV). Its characteristic UV absorption peak (conjugated diene structure) is usually in the range of 270-280 nm.
In addition to natural extraction, 13-oxo-9Z and 11E-ODE can also be obtained through chemical synthesis or enzymatic conversion. The chemical synthesis route usually starts with linoleic acid or 13-HODE, and converts the 13th hydroxyl group to a ketone group through selective oxidation reaction. The enzymatic conversion method utilizes the synergistic effect of lipoxygenase and hydroxy fatty acid dehydrogenase to prepare the target compound from linoleic acid through a two-step enzymatic reaction. The establishment of synthetic methods provides the possibility for large-scale preparation and structural modification.
Atherosclerosis is the main pathological basis of cardiovascular disease, and its occurrence and development are closely related to lipid metabolism disorder, endothelial dysfunction, inflammatory reaction and oxidative stress. The potential role of 13-oxo-9Z, 11E-ODE in the regulation of atherosclerosis has become a research hotspot.
Research shows that 13-oxo-9Z, 11E-ODE can regulate the formation of foam cells, which is the key event of early atherosclerosis. This compound inhibits the transformation of macrophages into foam cells by affecting the expression and function of scavenger receptors (such as LOX-1) and reducing the uptake of oxidized low-density lipoprotein (ox LDL). In addition, 13-oxo-9Z and 11E-ODE are also involved in regulating cholesterol reversal by upregulating the expression of ATP binding cassette transporter A1 (ABCA1), promoting intracellular cholesterol efflux, and reducing lipid deposition in arterial walls.
In vascular endothelial cells, 13-oxo-9Z and 11E-ODE exhibit protective effects, which can alleviate ox LDL induced endothelial damage, inhibit the expression of adhesion molecules, and thus reduce the migration and infiltration of monocytes to the subendothelial layer. These effects together constitute its multi target mechanism of anti atherosclerosis.
Inflammatory response plays a central role in the occurrence and development of various diseases. 13-oxo-9Z and 11E-ODE, as oxidative fatty acids, have the ability to regulate inflammatory responses. Research has found that this compound can inhibit lipopolysaccharide (LPS) - induced macrophage inflammatory response, reduce the production of pro-inflammatory cytokines (such as TNF - α, IL-6, IL-1 β), and upregulate the expression of anti-inflammatory factors (such as IL-10).
Its anti-inflammatory mechanism involves the regulation of multiple signaling pathways, including inhibition of the nuclear factor kappa B (NF - κ B) pathway, regulation of the mitogen activated protein kinase (MAPK) pathway, and activation of peroxisome proliferator activated receptors (PPARs). It is worth noting that the anti-inflammatory activity of 13-oxo-9Z and 11E-ODE is closely related to the conjugated dienone group in their structure, which can undergo Michael addition reactions with cysteine residues in proteins, thereby modifying the activity of key signaling proteins.
As intermediate products of fatty acid metabolism, 13-oxo-9Z and 11E-ODE play a regulatory role in energy metabolism and glucose and lipid metabolism. Research has shown that this compound can activate AMP activated protein kinase (AMPK), which is a key sensor of cellular energy metabolism. Its activation can promote glucose uptake, fatty acid oxidation, and mitochondrial biosynthesis, while inhibiting fat synthesis and gluconeogenesis.
In adipocytes, 13-oxo-9Z and 11E-ODE can regulate the secretion of adipokines and improve insulin sensitivity. In addition, the compound also affects liver lipid metabolism, reduces triglyceride accumulation, and may have a protective effect on non-alcoholic fatty liver disease.
Although 13-oxo-9Z and 11E-ODE are themselves oxidation products, they exhibit certain antioxidant activity. Research has found that this compound can scavenge free radicals, inhibit lipid peroxidation reactions, and protect cells from oxidative stress damage. Its antioxidant mechanism may be related to its conjugated diene structure, which can capture free radicals and form stable resonant hybrids.
In addition to the main activities mentioned above, 13-oxo-9Z and 11E-ODE also exhibit other potential pharmacological effects, including antiplatelet aggregation, vasodilation, and anti-tumor effects. The discovery of these activities has broadened the application prospects of the compound, but its specific mechanism and in vivo effectiveness still need further research and verification.
13-oxo-9Z and 11E-ODE exert their biological effects by acting on multiple molecular targets involved in lipid metabolism, inflammatory signaling, cell apoptosis, and energy metabolism.
LOX-1（OLR1）Lectin like oxidized low-density lipoprotein receptor-1 (LOX-1) is the main ox LDL receptor expressed on vascular endothelial cells and macrophages. 13-oxo-9Z, 11E-ODE can down regulate the expression of LOX-1, reduce the uptake of ox LDL, and thus inhibit the formation of foam cells. This effect may be achieved by interfering with the transcriptional regulation of LOX-1 or promoting its degradation.
AMPK（PRKAA1）AMPK is a core regulatory factor for cellular energy homeostasis. 13-oxo-9Z and 11E-ODE promote fatty acid oxidation and glucose metabolism by activating the AMPK signaling pathway, while inhibiting inflammatory responses and lipid synthesis. The activation of AMPK may be one of the key mechanisms by which this compound exerts metabolic regulation and anti-inflammatory effects.
EHMT2 Dyschromatin histone lysine N-methyltransferase 2 (EHMT2) is involved in epigenetic regulation. Research has shown that 13-oxo-9Z and 11E-ODE may regulate the expression of specific genes by affecting the activity of EHMT2, thereby affecting cell differentiation and function.
MCL1 and BCL2 MCL1 and BCL2 are members of the B-cell lymphoma 2 (BCL-2) family, regulating cell apoptosis. 13-oxo-9Z and 11E-ODE can regulate the expression of these anti apoptotic proteins, affecting the balance between cell survival and death. In atherosclerotic plaque, this effect may affect the stability and cell composition of plaque.
RECQ1 RECQ1 is a DNA helicase involved in DNA repair and maintaining genomic stability. The interaction between 13-oxo-9Z, 11E-ODE and RECQ1 may affect the DNA damage response and aging process of cells.
ABCA1 ATP binding cassette transporter A1 (ABCA1) mediates the transport of cholesterol from cells to apolipoprotein A-I, which is a key step in cholesterol reverse transport. 13-oxo-9Z, 11E-ODE up regulate the expression of ABCA1, promote cholesterol efflux, and reduce the formation of foam cells.
13-oxo-9Z and 11E-ODE exert their biological effects by regulating multiple signaling pathways:
NF - κ B pathway This compound inhibits the activity of I κ B kinase (IKK), reduces the phosphorylation and degradation of I κ B α, thereby inhibiting the nuclear translocation of NF - κ B and the transcription of pro-inflammatory genes.
MAPK pathway 13-oxo-9Z and 11E-ODE regulate the phosphorylation levels of MAPKs such as p38, JNK, and ERK, affecting inflammatory response, cell proliferation, and differentiation.
PPAR pathway As derivatives of fatty acids, 13-oxo-9Z and 11E-ODE may act as ligands for PPARs, activating PPAR α and PPAR γ, regulating the expression of genes related to lipid metabolism and inflammatory response.
Nrf2 pathway This compound can activate the nuclear factor E2 related factor 2 (Nrf2) signaling pathway, induce the expression of antioxidant enzymes, and enhance the antioxidant defense ability of cells.
The biological activity of 13-oxo-9Z and 11E-ODE is closely related to their chemical structure. The conjugated diene structure is a key pharmacophore group that can undergo reversible Michael addition reaction with cysteine thiol groups in proteins, forming covalent adducts and regulating protein function. The configuration of the 9Z, 11E conjugated double bond is crucial for activity, and changing the configuration or position of the double bond can significantly affect biological activity. The 13th keto group is another key functional group, and reducing it to a hydroxyl group (such as 13-HODE) or alkylating it can alter the activity and metabolic stability of the compound.
Based on computational chemistry and experimental data, the pharmacological characteristics of 13-oxo-9Z and 11E-ODE are as follows:
molecular weight：294.4350 Da， Meeting the molecular weight range of small molecule drugs (usually<500 Da) is beneficial for oral absorption and cell membrane penetration.
fat-soluble LogP is 4.6985, which is at a high level, indicating that the compound has good membrane permeability. However, excessive lipid solubility may lead to poor water solubility, metabolic instability, and increased toxicity.
Water solubility：0.0083 mg/mL， Belonging to extremely low water solubility compounds, this characteristic is the main factor limiting their oral bioavailability. Solubilization techniques such as nanoemulsions, liposomes, and cyclodextrin inclusion complexes are required in the development of formulations.
Blood-brain barrier penetration Predicted as high penetrability, this characteristic may be advantageous for treating central nervous system diseases, but also increases the risk of neurotoxicity.
safety HERG inhibition is negative, Ames test is negative, preliminary safety is good. But more in vitro and in vivo toxicology studies are needed to comprehensively evaluate its safety.
At present, there is insufficient systematic research on the pharmacokinetics of 13-oxo-9Z and 11E-ODE. However, based on their chemical structure and studies of similar compounds, the following characteristics can be inferred:
absorb As a derivative of long-chain fatty acids, it may be absorbed through the intestinal lymphatic system after oral administration, and the absorption process is influenced by the fat content in food. Low water solubility may lead to lower oral bioavailability.
distribution High lipid solubility makes it prone to bind with plasma proteins (such as albumin) and lipoproteins, and widely distributed in lipid rich tissues such as adipose tissue, liver, and brain tissue.
Metabolism This compound may undergo multiple metabolic pathways, including β - oxidation (shortening of carbon chain), reduction (reduction of 13 keto group to hydroxyl group), conjugation reaction (binding with glucuronic acid or sulfuric acid), etc. Metabolites may have different biological activities.
excretion Metabolites are mainly excreted through urine and bile, with less excretion of the prototype drug.
Regarding the pharmaceutical challenges of 13-oxo-9Z and 11E-ODE, the following formulation strategies can be considered:
Based on the multi-target mechanism of 13-oxo-9Z, 11E-ODE in atherosclerosis, this compound has the potential to be developed as an anti atherosclerosis drug. It may provide therapeutic effects superior to single target drugs by regulating multiple targets such as LOX-1, ABCA1, AMPK, while affecting lipid metabolism, inflammatory response, and endothelial function. In addition, as an endogenous metabolite, this compound may have good safety and tolerability.
The AMPK activation and metabolic regulation function of 13-oxo-9Z, 11E-ODE make it have potential application value in the treatment of metabolic diseases such as type 2 diabetes, obesity and non-alcoholic fatty liver disease. By improving insulin sensitivity, promoting energy expenditure, and inhibiting fat synthesis, this compound may become part of a comprehensive treatment strategy for metabolic syndrome.
The anti-inflammatory activity of this compound suggests its potential application in chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Its unique anti-inflammatory mechanism (involving NF - κ B, MAPK, and PPAR pathways) may provide a complementary or alternative option to existing anti-inflammatory drugs.
Given that 13-oxo-9Z and 11E-ODE have high blood-brain barrier penetration ability and antioxidant and anti-inflammatory activities, their potential roles in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are worth exploring. This compound may exert neuroprotective effects by alleviating pathological processes such as neuroinflammation, oxidative stress, and protein aggregation.
Although 13-oxo-9Z and 11E-ODE exhibit various pharmacological activities and application prospects, their development still faces many challenges:
Pharmacokinetic optimization Low water solubility and potential rapid metabolism are the main obstacles limiting its clinical application, requiring the development of effective formulation strategies or structural modifications.
Target selectivity This compound acts on multiple targets, which may lead to off target effects and unpredictable biological reactions. Further research is needed on its target selectivity and dose-response relationship.
In vivo effectiveness verification The current research is mainly based on in vitro experiments and animal models, and its effectiveness and safety in humans still need to be validated through clinical trials.
Source and Cost Natural extraction yields are low, chemical synthesis costs are high, and efficient and economical preparation methods need to be developed.
Future research directions should include: in-depth elucidation of the molecular mechanism of action of the compound, particularly its interaction mode with key target proteins; Conduct systematic pharmacokinetic and toxicological studies; Developing new formulations to improve bioavailability; Explore the structure activity relationship and design derivatives with better drug properties; And conduct translational medicine research to evaluate its therapeutic potential in disease models and clinical settings.
(9Z, 11E) -13-oxo-9,11-octadecadienoic acid, as a natural oxidized fatty acid with a unique conjugated diene structure, plays important biological functions in both plants and mammals. This article systematically reviews the research progress on the chemical structure, physicochemical properties, plant origin, extraction methods, pharmacological activity, mechanism of action, molecular targets, and pharmacological evaluation of the compound. 13-oxo-9Z, 11E-ODE regulate NF - κ B, MAPK, PPAR and other signal pathways by acting on multiple molecular targets such as LOX-1, AMPK, ABCA1, etc., and show multiple pharmacological activities in anti atherosclerosis, anti-inflammatory, metabolic regulation, antioxidant and other aspects.
As an endogenous metabolite, this compound has a good safety basis, but its low water solubility and potential metabolic instability are key factors that restrict its pharmacological properties. Future research needs to further elucidate its mechanism of action, improve its pharmacokinetic characteristics through formulation optimization and structural modification, and promote the transformation of this natural product from laboratory research to clinical application. With the continuous deepening of understanding of the role of lipid signaling molecules in the occurrence and development of diseases, 13-oxo-9Z and 11E-ODE are expected to become important lead compounds for the development of new therapeutic drugs, providing new strategies and choices for the treatment of cardiovascular diseases, metabolic diseases, and inflammatory diseases.
Batch can search by a CAS number,one per line
