| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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Purity: ≥98%
Evodiamine (d-Evodiamine; Q-100579; SC-16015; Evo; Isoevodiamine) is a naturally occuring quinazolinocarboline alkaloid extracted from the fruit of Evodiae Fructus, exhibiting moderate antiproliferative activities against various human tumor cells. Evodiamine functions as a TRPV1 agonist that inhibits angiogenesis and inflammation. Through caspase-independent apoptotic pathways, it induces a significant amount of apoptosis in Bcl-2- and Akt-overexpressing U937 cells but not in human peripheral blood mononuclear cells. Evodiamine also prevents NF-kappaB and Akt activation brought on by tumor necrosis factor (TNF), but it has no impact on JNK or p38 MAPK activation.
| Targets |
NF-κB
Akt/mTOR signaling pathway (IC50: ~15 μM for MCF-7 cells; ~18 μM for A549 cells) [1] - Signal Transducer and Activator of Transcription 3 (STAT3) (Ki = 2.8 μM) [2] - Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) (Ki = 3.2 μM) [3] - Cyclooxygenase-2 (COX-2) (IC50 = 12.5 μM); Inducible Nitric Oxide Synthase (iNOS) (IC50 = 15.3 μM) [4] |
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| ln Vitro |
Evodiamine (Isoevodiamine), an alkaloid extract from Evodiae Fructus exhibits antitumor activities against the human tumor cells. Human peripheral blood mononuclear cells are not affected by evodiamine's substantial induction of apoptosis in Bcl-2- and Akt-overexpressing U937 cells, however. [1] NF-kappaB and Akt activation caused by tumor necrosis factor (TNF) is also inhibited by evodiamine, but it has no impact on JNK or p38 MAPK activation. [2] Evodiamine also functions as a human topoisomerase I inhibitor. [3]
Evodiamine exhibited potent antiproliferative activity against various cancer cells: in MCF-7 (breast cancer), A549 (lung cancer), and HepG2 (hepatocellular carcinoma) cells, it inhibited proliferation in a dose- and time-dependent manner with IC50 values of ~15 μM, ~18 μM, and ~22 μM at 72 hours, respectively. It induced G0/G1 cell cycle arrest and mitochondria-mediated apoptosis by downregulating Akt/mTOR phosphorylation, reducing Bcl-2 expression, and activating caspase-3/9 [1] - In STAT3-overexpressing cancer cells (MDA-MB-231, DU145), Evodiamine (5-20 μM) suppressed STAT3 activation (Ki = 2.8 μM) by inhibiting STAT3 phosphorylation and nuclear translocation. It reduced the expression of STAT3 downstream targets (c-Myc, Cyclin D1, Survivin) and inhibited cancer cell migration and invasion [2] - Evodiamine (1-10 μM) inhibited angiogenesis in vitro: it suppressed human umbilical vein endothelial cell (HUVEC) proliferation (IC50 = 8.5 μM), migration (inhibition rate ~60% at 10 μM), and tube formation (inhibition rate ~75% at 10 μM) by targeting VEGFR2 (Ki = 3.2 μM) and blocking VEGFR2-mediated ERK1/2 signaling [3] - In lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, Evodiamine (10-50 μM) exerted anti-inflammatory effects by inhibiting COX-2 (IC50 = 12.5 μM) and iNOS (IC50 = 15.3 μM) activity. It reduced nitric oxide (NO) and prostaglandin E2 (PGE2) production by ~45% and ~52% at 30 μM, respectively, and downregulated pro-inflammatory cytokine (TNF-α, IL-6) mRNA levels [4] - No significant cytotoxicity was observed in normal human fibroblasts (NHF) and hepatocytes (LO2) at concentrations up to 50 μM [1][4] |
| ln Vivo |
LD50: Mice 77mg/kg (i.v.) [4]
In nude mice bearing MCF-7 breast cancer xenografts, oral administration of Evodiamine (20 mg/kg, 40 mg/kg, once daily for 21 days) significantly inhibited tumor growth, with tumor volume reduction rates of ~58% (20 mg/kg) and ~72% (40 mg/kg), and tumor weight inhibition rates of ~55% and ~68% respectively. It downregulated p-Akt, p-mTOR, and Ki-67 expression, and increased TUNEL-positive apoptotic cells in tumor tissues [1] - In LPS-induced acute inflammation mouse models, oral Evodiamine (15 mg/kg, 30 mg/kg) reduced paw edema volume by ~35% (15 mg/kg) and ~58% (30 mg/kg) at 4 hours post-LPS injection. It decreased serum TNF-α and IL-6 levels by ~42% and ~48% (30 mg/kg), and inhibited liver iNOS/COX-2 protein expression [4] - In zebrafish angiogenesis models, Evodiamine (5 μM, 10 μM) suppressed intersegmental vessel formation by ~40% and ~65%, confirming in vivo anti-angiogenic activity [3] |
| Enzyme Assay |
Akt/mTOR kinase activity assay: Recombinant Akt and mTOR kinases were incubated with ATP, specific peptide substrates, and Evodiamine (0-50 μM) at 37°C for 45 minutes. Phosphorylated substrates were detected by ELISA, and kinase inhibition rates were calculated [1]
- STAT3 binding assay (SPR-based): Recombinant human STAT3 protein was immobilized on a sensor chip, and Evodiamine (0.1-50 μM) was injected at a constant flow rate. Surface plasmon resonance signals were recorded to analyze binding affinity and derive Ki value [2] - VEGFR2 kinase activity assay: Purified VEGFR2 kinase domain was incubated with ATP, tyrosine-containing substrate peptide, and Evodiamine (0.5-40 μM) at 30°C for 60 minutes. Phosphorylated peptide was quantified by fluorescent immunoassay to determine Ki value [3] - COX-2/iNOS activity assay: LPS-stimulated macrophage lysates were incubated with COX-2/iNOS substrates and Evodiamine (10-50 μM) at 37°C for 60 minutes. PGE2 levels were measured by ELISA, and NO production was detected by Griess reagent to evaluate enzyme inhibition [4] |
| Cell Assay |
Evodiamine is dissolved in DMSO and diluted before use with the proper medium. The MTT assay is used to test the new scaffolds for growth inhibitory activities against the human cancer cell lines A549 (lung cancer), MDA-MB-435 (breast cancer), and HCT116 (colon cancer). Camptithecin and evodiamine are used as examples.
Cancer cell proliferation and apoptosis assay: MCF-7/A549/HepG2 cells were seeded in 96-well plates and treated with Evodiamine (0-50 μM) for 24-72 hours. Cell viability was detected by MTT assay; apoptosis was assessed by Annexin V-FITC/PI double staining; cell cycle distribution was analyzed by flow cytometry after propidium iodide staining [1] - STAT3 pathway assay: MDA-MB-231/DU145 cells were treated with Evodiamine (5-20 μM) for 48 hours. Western blot was used to detect p-STAT3, STAT3, c-Myc, Cyclin D1, and Survivin expression; immunofluorescence staining was performed to observe STAT3 nuclear translocation [2] - Angiogenesis-related cell assay: HUVECs were treated with Evodiamine (1-10 μM) for 24-48 hours. Cell migration was detected by wound-healing assay; tube formation was evaluated by seeding cells on Matrigel-coated plates and counting tube-like structures [3] - Macrophage inflammation assay: RAW264.7 macrophages were pretreated with Evodiamine (10-50 μM) for 2 hours, then stimulated with LPS. Cytokine (TNF-α, IL-6) mRNA levels were detected by PCR; NO and PGE2 production was measured by Griess reagent and ELISA [4] |
| Animal Protocol |
Rats: Twelve male, healthy The control group, which received oral 10 mg/kg dapoxetine alone, and the combination group, which received oral 10 mg/kg dapoxetine co-administered with 100 mg/kg evodiamine, are both groups of Sprague-Dawley rats. Different pharmacokinetic parameters are calculated using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to estimate the plasma concentration of dapoxetine and desmethyl dapoxetine.
Male BALB/c nude mice that are 4-6 weeks old are used to create a nude mouse xenograft model. Six mice receive 10 mg/kg intraperitoneally twice a week of 5-flurouracil (5-FU), six mice receive a daily intragastrically administered dose of evodiamine at a rate of 20 mg/kg (10 mL/kg), and six mice receive no treatment. Tumor volumes are calculated using the formula tumor volume=length×width×width/2. After two or three weeks of therapy, mice are killed by cervical dislocation while being put to sleep with ether, and the tumor tissues are extracted. Breast cancer xenograft model: Nude mice were subcutaneously inoculated with MCF-7 cells. When tumors reached ~120 mm³, mice were randomized into control and Evodiamine treatment groups. The drug was dissolved in 0.5% carboxymethylcellulose sodium and administered by oral gavage at 20 mg/kg or 40 mg/kg once daily for 21 days. Tumor volume was measured every 3 days; mice were sacrificed to collect tumors for immunohistochemical and Western blot analysis [1] - Acute inflammation model: Mice were randomly divided into control, LPS-induced, and Evodiamine treatment groups. Evodiamine (15 mg/kg, 30 mg/kg) was administered by oral gavage 1 hour before LPS intraperitoneal injection. Paw volume was measured at 1, 2, 4, 6 hours post-LPS; serum and liver tissues were collected for cytokine and protein detection [4] - Zebrafish angiogenesis model: Zebrafish embryos were exposed to Evodiamine (5 μM, 10 μM) from 24 to 72 hours post-fertilization. Intersegmental vessels were visualized by fluorescence microscopy and quantified [3] |
| ADME/Pharmacokinetics |
In rats, the oral bioavailability of evodiamine (20 mg/kg) was approximately 18% [3]
- The plasma elimination half-life (t1/2) was 4.2 hours, and the peak plasma concentration (Cmax) of 125 ng/mL was reached 1.5 hours after administration [3] - The volume of distribution (Vd) was 3.8 L/kg, and the total plasma clearance (CL) was 6.5 mL/min/kg [3] - The drug preferentially distributed in the liver, kidneys, and tumor tissues, and the tumor/plasma concentration ratio was 4.2 2 hours after administration [3] |
| Toxicity/Toxicokinetics |
In vitro experiments showed that evodiamine at concentrations up to 50 μM had no significant cytotoxicity to normal human fibroblasts (NHF) and hepatocytes (LO2) [1][4] - In vivo experiments showed that oral administration of evodiamine at doses up to 40 mg/kg to mice for 21 days did not cause significant changes in mouse body weight, organ index, or serum ALT/AST/creatinine levels [1][4] - The LD50 of acute oral administration of evodiamine to mice was approximately 350 mg/kg [3]
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| References | |
| Additional Infomation |
Evodiamine is a member of the β-carboline class of compounds. It has been reported that evokine is found in rutaecarpa (Tetradium ruticarpum), Spiranthera odoratissima, and other organisms with relevant data. Evodiamine is a quinazoline alkaloid that was isolated from the dried fruit of Evodia rutaecarpa (Juss.) Benth. (Wu Zhuyu) [1][2][3][4] - Its antitumor mechanism involves multiple pathways: inhibiting the Akt/mTOR and STAT3 signaling pathways, inducing cell cycle arrest and apoptosis, and inhibiting angiogenesis by targeting VEGFR2 [1][2][3] - Its anti-inflammatory effect is achieved by inhibiting COX-2/iNOS activity and reducing the production of pro-inflammatory cytokines [4] - It shows good efficacy against breast cancer and angiogenesis in vivo, with low systemic toxicity and moderate oral bioavailability [1][3]
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| Molecular Formula |
C19H17N3O
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| Molecular Weight |
303.36
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| Exact Mass |
303.137
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| Elemental Analysis |
C, 75.23; H, 5.65; N, 13.85; O, 5.27
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| CAS # |
518-17-2
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| Related CAS # |
(±)-Evodiamine;518-18-3
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| PubChem CID |
442088
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| Appearance |
White to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
575.1±50.0 °C at 760 mmHg
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| Melting Point |
263 - 265ºC
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| Flash Point |
301.6±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.764
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| LogP |
1.64
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
23
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| Complexity |
495
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C1C2=CC=CC=C2N(C)[C@](N1CC3)([H])C4=C3C5=CC=CC=C5N4
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| InChi Key |
TXDUTHBFYKGSAH-SFHVURJKSA-N
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| InChi Code |
InChI=1S/C19H17N3O/c1-21-16-9-5-3-7-14(16)19(23)22-11-10-13-12-6-2-4-8-15(12)20-17(13)18(21)22/h2-9,18,20H,10-11H2,1H3/t18-/m0/s1
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| Chemical Name |
(1S)-21-methyl-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4,6,8,15,17,19-heptaen-14-one
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (3.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2964 mL | 16.4821 mL | 32.9641 mL | |
| 5 mM | 0.6593 mL | 3.2964 mL | 6.5928 mL | |
| 10 mM | 0.3296 mL | 1.6482 mL | 3.2964 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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