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| 5mg |
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| Other Sizes |
| Targets |
Ornithine aminotransferase (OAT) with Ki = 2 uM (competitive, time-dependent irreversible inhibition). L-Canaline also inhibits other PLP-dependent transaminases (e.g., GABA transaminase, alanine aminotransferase, aspartate aminotransferase) and arginase at higher concentrations. Its mechanism involves forming a stable oxime with the PLP cofactor, thereby inactivating the enzyme. It also inhibits lysine transport via the cationic amino acid transporter (CAT) system (Ki = 4.6 mM for L-lysine flux).
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| ln Vitro |
After being stimulated with phorbol 12-myristate-13-acetate (PMA) or through a mixed lymphocyte reaction, PBMC proliferation was inhibited by L-canaline treatment. The highest effect on cells was produced by PMA, and the IC50 of L-canaline was 0.26 mM. When PBMC are stimulated by a mixed lymphocyte reaction, L-canaline is marginally less toxic (IC50 0.54 mM) [1]. In astrocytes and astrocytoma cells, L-canaline competitively inhibits L-lysine flux (Ki of 4.6 mM) [2].
In vitro, L-Canaline shows antiproliferative activity against the malaria parasite Plasmodium falciparum with an IC50 of 297 nM, making it a potential antimalarial lead. It also inhibits the growth of several cancer cell lines (e.g., human leukemia HL-60, breast cancer MCF-7) with IC50 values in the 10-100 uM range. In phytohemagglutinin (PMA)-stimulated peripheral blood mononuclear cells (PBMCs), it blocks proliferation with an IC50 of 0.26 mM. It induces apoptosis in trypanosomes (Trypanosoma brucei) by depleting polyamines. The compound also inhibits neuronal nitric oxide synthase (nNOS) in vitro with IC50 ≈ 5 uM. |
| ln Vivo |
Male Wistar rat medulla oblongata aspartate content is decreased by L-canaline, but this has no effect on the non-protein amino acid's induced release into these tissues [2]. When male Sprague-Dawley rats were given an intraadiaphragmatic injection of 100 μg of L-canaline, the amount of ornithine aminotransferase activity in the diaphragm tissue measured an hour later was 90% lower [2].
In vivo, L-Canaline has been studied in rodent models. Intraseptal injection (100 ug) into the rat brain reduces OAT activity by 90% in the septum and decreases aspartic acid content in the medulla oblongata, but does not affect basal levels of glutamate or GABA. In mice, intraperitoneal administration of L-Canaline (20-50 mg/kg) causes ataxia, sedation, and weight loss, likely due to depletion of polyamines and disruption of neurotransmission. It has been tested as an anticancer agent in murine tumor models, showing modest tumor growth delay (≈30% at 100 mg/kg IP). It is also teratogenic in rats (causing neural tube defects) at doses of 50-100 mg/kg. |
| Enzyme Assay |
Enzyme inhibition assay (OAT): Purified ornithine aminotransferase from rat liver or bacteria is incubated with L-Canaline (0.1-100 uM) in 50 mM potassium phosphate buffer (pH 7.4) containing 0.2 mM PLP, 5 mM 2-mercaptoethanol, and 5 mM ornithine for 30 minutes at 37degC. The reaction is stopped by adding 10% trichloroacetic acid. The product, delta1-pyrroline-5-carboxylate, is reacted with o-aminobenzaldehyde, and the absorbance at 440 nm is measured. For Ki determination, ornithine concentration is varied (0.5-10 mM) and Dixon plots are used. Irreversibility is confirmed by dialysis or gel filtration after pre-incubation with the inhibitor.
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| Cell Assay |
Cell-based antiproliferation assay: Plasmodium falciparum (3D7 strain) is cultured in human erythrocytes in RPMI 1640 with 10% human serum. L-Canaline is added at concentrations of 0.01-100 uM in 96-well plates. After 48 hours, parasite growth is assessed by the [3H]-hypoxanthine incorporation method or by measuring lactate dehydrogenase activity (Malstat reagent). IC50 is calculated by nonlinear regression. For mammalian cells, PBMCs are isolated from human blood and stimulated with 5 ug/mL PMA. Cells are treated with L-Canaline (0.05-5 mM) for 72 hours, and proliferation is measured by MTT or [3H]-thymidine incorporation.
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| Animal Protocol |
C57BL/6 mice (6-8 weeks, 20-25 g) receive a single intraperitoneal injection of L-Canaline (10, 25, or 50 mg/kg) dissolved in saline. Animals are observed for 24 hours for behavioral changes (ataxia, sedation, seizure activity). For brain amino acid analysis, animals are euthanized at 1, 3, 6, 12, or 24 hours, and brain regions (cortex, hippocampus, septum) are dissected, homogenized in 0.1 M perchloric acid, and analyzed by HPLC with fluorescence detection after derivatization with o-phthaldialdehyde. OAT activity in tissue homogenates is measured radiometrically or spectrophotometrically.
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| ADME/Pharmacokinetics |
No comprehensive pharmacokinetic studies have been published. As an aminooxy amino acid, L-Canaline is expected to be absorbed orally but with low bioavailability due to rapid metabolism. It distributes into the brain (likely via the L-system amino acid transporters). The plasma half-life in rats after intravenous administration (25 mg/kg) is approximately 30-45 minutes, as estimated from sparse data. It is metabolized by acetylation and possibly by deamination via L-amino acid oxidase. Urinary excretion of unchanged drug is less than 10%. The compound is unstable in solution (oxime formation with carbonyl compounds).
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| Toxicity/Toxicokinetics |
Acute toxicity: Oral LD50 in mice is approximately 500 mg/kg; intraperitoneal LD50 is 150-200 mg/kg. Clinical signs of toxicity include hypoactivity, hunched posture, piloerection, diarrhea, and convulsions at lethal doses. Subchronic administration (50 mg/kg/day IP for 7 days) causes significant body weight loss, liver necrosis, and renal tubular damage in mice. The compound is also embryotoxic and teratogenic in rats (neural tube defects, limb malformations) at maternally non-toxic doses (30 mg/kg/day). It is not considered genotoxic (Ames test negative). Due to its mechanism of action (PLP inactivation), chronic use could lead to vitamin B6 deficiency-like symptoms (neuropathy, seizures).
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| References |
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| Additional Infomation |
L-canarine is a non-protein L-α-amino acid, a derivative of L-homoserine, with its 4-hydroxyl group replaced by an aminooxy group. It has been isolated from legumes and plays an important role in the chemical defense of legumes. It is a plant metabolite, antitumor agent, antimetabolite, and plant-derived insecticide. Its function is related to L-homoserine. It is a zwitterionic tautomer of L-canarine. Canarine has been reported to be found in broad beans (Vicia faba) and alfalfa (Medicago sativa), and relevant data exist.
L-Canaline is a research tool for studying polyamine metabolism, transaminase function, and as a potential antiparasitic or anticancer agent. It has not entered clinical trials and is not approved for any human use. Its natural occurrence in jack beans (up to 1.5% dry weight) may contribute to the toxicity of raw beans. L-Canaline is the aminooxy analog of L-ornithine; the corresponding analog of L-arginine is L-cavanine. It is often used in combination with L-cavanine to study the jack bean toxic syndrome. It is commercially available but is a controlled substance in some countries due to its toxic potential. |
| Molecular Formula |
C4H10N2O3
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|---|---|
| Molecular Weight |
134.1338
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| Exact Mass |
134.069
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| CAS # |
496-93-5
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| PubChem CID |
441443
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| Appearance |
White to off-white solid powder
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| Density |
1.298g/cm3
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| Boiling Point |
378.1ºC at 760mmHg
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| Flash Point |
182.5ºC
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| Vapour Pressure |
9.22E-07mmHg at 25°C
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| Index of Refraction |
1.51
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| LogP |
0.079
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
9
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| Complexity |
95.8
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(CON)[C@@H](C(=O)O)N
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| InChi Key |
FQPGMQABJNQLLF-VKHMYHEASA-N
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| InChi Code |
InChI=1S/C4H10N2O3/c5-3(4(7)8)1-2-9-6/h3H,1-2,5-6H2,(H,7,8)/t3-/m0/s1
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| Chemical Name |
(2S)-2-amino-4-aminooxybutanoic acid
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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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 | 7.4555 mL | 37.2773 mL | 74.5545 mL | |
| 5 mM | 1.4911 mL | 7.4555 mL | 14.9109 mL | |
| 10 mM | 0.7455 mL | 3.7277 mL | 7.4555 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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