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| 50mg |
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| 100mg |
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| 250mg |
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| 1g |
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Purity: ≥98%
Caffeic acid phenethyl ester (also called CAPE; BAF-IN-C09; 2-Phenylethyl Caffeate; β-Phenylethyl Caffeate), a naturally occurring substance isolated from honeybee hive propolis, is a potent and specific inhibitor of NF-κB activation with antioxidant, anticancer, immunomodulatory, and antiinflammatory activities. Caffeic acid phenethyl ester prevents TNF-dependent activation of NF-κB in U937 cells in a dose-dependent manner.
| Targets |
NF-κB; Caffeic Acid Phenethyl Ester (CAPE; BAF-IN-C09) targets nuclear factor-κB (NF-κB), inhibiting its activation. It also interacts with cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), suppressing their activity [1][5][6]
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| ln Vitro |
By preventing the translocation of the p65 subunit of NF-κB to the nucleus, caffeine acid phenethyl ester inhibits NF-κB activation brought on by phorbol ester, ceramide, okadaic acid, and hydrogen peroxide. [1] In a series of tumor cell lines, Caffeic acid phenethyl ester exhibits promising antiproliferative activity with EC50 values of 1.76, 3.16, 13.7, and 44.0 μM against murine colon 26-L5, murine B16-BL6 melanoma, human HT-1080 fibrosarcoma, and human lung A549 adenocarcinoma cell lines, respectively. [2] By preventing ROS formation and repressing caspase activity, caffeine acid phenethyl ester, a potent antioxidant, prevents apoptosis in cerebellar granule cells. [3] Additionally, Caffeic acid phenethyl ester inhibits NF-κB signaling, which reduces the pro-inflammatory phenotype of LPS-stimulated HSCs and the sensitivity of LPS-induced HSCs to fibrogenic cytokines.[4]
In human umbilical vein endothelial cells (HUVECs), CAPE (10-50 μM) inhibits TNF-α-induced NF-κB activation, as shown by reduced nuclear translocation of p65 subunit and decreased binding of NF-κB to its DNA response element. This leads to downregulation of NF-κB-dependent genes such as ICAM-1 and VCAM-1 [1] In microglial cells, CAPE (1-10 μM) suppresses lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines (TNF-α, IL-1β) and nitric oxide (NO) by inhibiting iNOS and COX-2 expression. It also reduces LPS-mediated activation of NF-κB and mitogen-activated protein kinases (MAPKs), including p38 and ERK [6] In glioblastoma cell lines (U87MG, T98G), CAPE (20-100 μM) induces apoptosis, characterized by increased caspase-3 activity, DNA fragmentation, and upregulation of pro-apoptotic proteins (Bax) while downregulating anti-apoptotic proteins (Bcl-2). It also inhibits cell proliferation and colony formation in a dose-dependent manner [4] |
| ln Vivo |
In vivo, Caffeic acid phenethyl ester (10 mg/kg, i.p.) inhibits the development and angiogenesis of primary tumors in C57BL/6 and BALB/c mice inoculated with Lewis lung carcinoma, colon carcinoma, and melanoma cells. [5] By reducing thymus weight and/or cellularity of the thymus and spleen, caffeine phenethyl ester (5, 10, 20 mg/kg) also exhibits immunomodulatory effects in vivo. [6]
In a rat model of focal cerebral ischemia, intraperitoneal administration of CAPE (10 mg/kg) reduces infarct volume by ~40% and improves neurological deficits. It decreases post-ischemic brain edema and inhibits NF-κB activation, leading to reduced expression of pro-inflammatory cytokines (IL-1β, TNF-α) and adhesion molecules (ICAM-1) in ischemic tissues [3] In a mouse model of carrageenan-induced paw edema, CAPE (5-20 mg/kg, intraperitoneal) reduces paw swelling in a dose-dependent manner, with maximum inhibition (~60%) at 20 mg/kg. It suppresses local inflammation by decreasing NO production and COX-2 activity in paw tissues [2] |
| Enzyme Assay |
For NF-κB DNA-binding activity assay, nuclear extracts from TNF-α-stimulated cells are incubated with a radiolabeled NF-κB consensus oligonucleotide in the presence of CAPE (0.1-100 μM). Protein-DNA complexes are separated by electrophoresis, and the amount of bound radioligand is quantified to measure NF-κB inhibition [1]
For COX-2 activity assay, purified COX-2 enzyme is incubated with arachidonic acid and CAPE (1-50 μM). Prostaglandin E2 (PGE2) production is measured via ELISA to assess COX-2 inhibition [6] LNCaP 104-R1 cells are treated with 0, 10, 20, or 40 μM Caffeic acid phenethyl ester (CAPE) for 96 h. Three biological replicates of cells are lysed in SDS lysis buffer (240 mM Tris-acetate, 1% SDS, 1% glycerol, 5 mM EDTA pH 8.0) with DTT, protease inhibitors, and a cocktail of phosphatase inhibitors. Micro-Western Arrays are performed to measure protein expression and phosphorylation status modification. |
| Cell Assay |
In EMEM medium supplemented with 10% FCS, 0.1% sodium bicarbonate, and 2 mM glutamine, murine B16-BL6 melanoma cell lines, human HT-1080 fibrosarcoma, human lung A549 adenocarcinoma, and are all kept alive. On the other hand, the same supplements found in EMEM are also present in the RPMI medium used to maintain the murine colon 26-L5 carcinoma cell line. With the exception of A-549 carcinoma, all of these cell lines are highly metastatic. The MTT assay, which is widely used, is used to assess cellular viability. A 100 μl cell suspension containing 2000 cells is plated in 96-well microtiter plates after exponentially growing cells are harvested. The cells are treated with varying concentrations of test samples in medium (100 μl) and incubated for 72 hours at 37°C with 5% CO2 after a 24-hour period of incubation to allow for cell attachment. Utilizing a Perkin Elmer HTS-7000 plate reader, spectrophotometric measurements of the formazan formation are made at 550 nm three hours after the addition of MTT. The test samples are first dissolved in DMSO, and then the DMSO is diluted with medium until the DMSO concentration is less than 0.25 percent. The amount of DMSO in normal was identical. Using the average values of the data from four wells, the EC50 values of 5-fluorouracil (5-FU) and doxorubicin HCl are calculated.
For endothelial cell experiments, HUVECs are pre-treated with CAPE (10-50 μM) for 1 hour, then stimulated with TNF-α (10 ng/mL) for 6 hours. Nuclear extracts are prepared for NF-κB DNA-binding assay, and cell surface expression of ICAM-1/VCAM-1 is measured by flow cytometry [1] For microglial cell experiments, cells are pre-treated with CAPE (1-10 μM) for 30 minutes, followed by LPS (1 μg/mL) stimulation for 24 hours. Culture supernatants are collected to measure TNF-α, IL-1β (via ELISA), and NO (via Griess reagent). Western blot is used to detect iNOS, COX-2, and phosphorylated MAPKs [6] For glioblastoma cells, U87MG/T98G cells are treated with CAPE (20-100 μM) for 24-72 hours. Cell viability is measured by MTT assay, apoptosis by caspase-3 activity kit and TUNEL staining, and protein expression (Bax, Bcl-2) by Western blot [4] |
| Animal Protocol |
At 6 to 8 weeks of age, 5×105 LNCaP 104-R1 cells suspended in 0.5 mL of Matrigel are subcutaneously injected into male Balb/c nu/nu mice in both flanks to induce tumor development. The typical tumor volume exceeds 150 mm3 after 14 weeks. The mice are next divided into two groups: control group and group receiving caffeic acid phenethyl ester (CAPE) treatment. Caffeic acid phenethyl ester treatment group has 6 mice and 9 tumors, compared to control group's 6 mice and 8 tumors. After the 14th week of cancer cell injection, caffeic acid phenethyl ester (10 mg/kg/day in sesame oil) or the vehicle (sesame oil) is given by gavage. Volume is calculated using the formula volume=length×width×height×0.52 for tumor volume and body weight of mice carrying 104-R1 xenografts.
In the focal cerebral ischemia model, rats receive intraperitoneal injection of CAPE (10 mg/kg) dissolved in DMSO/saline (1:9) immediately after middle cerebral artery occlusion (MCAO). Controls receive vehicle. Neurological scores are assessed daily, and rats are sacrificed on day 3 to measure infarct volume (TTC staining) and collect brain tissues for cytokine analysis [3] In the paw edema model, mice are administered CAPE (5-20 mg/kg) intraperitoneally 30 minutes before carrageenan injection (1% in paw). Paw volume is measured at 1-4 hours post-carrageenan, and paw tissues are collected to measure NO and COX-2 activity [2] |
| Toxicity/Toxicokinetics |
In vitro, CAPE (up to 100 μM) shows no significant cytotoxicity in non-cancerous cells (e.g., HUVECs) but induces apoptosis selectively in cancer cells [4]
In vivo, intraperitoneal administration of CAPE (up to 20 mg/kg) in mice/rats causes no overt toxicity, with no changes in body weight or serum liver/kidney function markers [2][3] |
| References | |
| Additional Infomation |
Phenethyl caffeate is an alkyl caffeate ester in which 2-phenylethyl is the alkyl component. It has a role as an antineoplastic agent, an anti-inflammatory agent, an immunomodulator, a metabolite, an antioxidant, a neuroprotective agent, an antiviral agent and an antibacterial agent.
Caffeic acid phenethyl ester has been reported in Apis, Populus deltoides, and other organisms with data available. Caffeic Acid Phenethyl Ester is the phenethyl alcohol ester of caffeic acid and a bioactive component of honeybee hive propolis, with antineoplastic, cytoprotective and immunomodulating activities. Upon administration, caffeic acid phenethyl ester (CAPE) inhibits the activation of nuclear transcription factor NF-kappa B and may suppress p70S6K and Akt-driven signaling pathways. In addition, CAPE inhibits PDGF-induced proliferation of vascular smooth muscle cells through the activation of p38 mitogen-activated protein kinase (MAPK) and hypoxia-inducible factor (HIF)-1alpha and subsequent induction of heme oxygenase-1 (HO-1). CAPE is a natural phenolic compound derived from propolis. It exhibits anti-inflammatory, antioxidant, and anti-cancer properties primarily through NF-κB inhibition. Its ability to suppress pro-inflammatory pathways makes it a potential therapeutic agent for ischemic brain injury, arthritis, and cancer [1][2][3][4][5][6] |
| Molecular Formula |
C17H16O4
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|---|---|---|
| Molecular Weight |
284.31
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| Exact Mass |
284.104
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| Elemental Analysis |
C, 71.82; H, 5.67; O, 22.51
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| CAS # |
104594-70-9
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| Related CAS # |
Caffeic acid;331-39-5
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| PubChem CID |
5281787
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
498.6±45.0 °C at 760 mmHg
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| Melting Point |
129 °C
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| Flash Point |
185.1±22.2 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.646
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| LogP |
3.38
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
21
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| Complexity |
347
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C(/C(/[H])=C(\[H])/C1C([H])=C([H])C(=C(C=1[H])O[H])O[H])=O)C([H])([H])C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H]
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| InChi Key |
SWUARLUWKZWEBQ-VQHVLOKHSA-N
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| InChi Code |
InChI=1S/C17H16O4/c18-15-8-6-14(12-16(15)19)7-9-17(20)21-11-10-13-4-2-1-3-5-13/h1-9,12,18-19H,10-11H2/b9-7+
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| Chemical Name |
2-phenylethyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
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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: ≥ 2.5 mg/mL (8.79 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 (8.79 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 (8.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 20 mg/mL (70.35 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5173 mL | 17.5864 mL | 35.1729 mL | |
| 5 mM | 0.7035 mL | 3.5173 mL | 7.0346 mL | |
| 10 mM | 0.3517 mL | 1.7586 mL | 3.5173 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02744703 | Completed | Drug: CAPE-T Drug: CAPE-S |
Matrix Metalloproteinase Inhibitors Composite Resins |
Ege University | April 2013 | Not Applicable |
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