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| Targets |
alpha-Cembrenediol has been identified as a potent inhibitor of the Epstein-Barr virus (EBV). It specifically inhibits the expression of EBV early antigens (EAs), which are viral proteins expressed during the lytic phase of the viral lifecycle. By inhibiting these antigens, alpha-CBD can suppress EBV replication and the production of new viral particles. It also has direct antitumor effects. It has been shown to suppress the growth of human cancer cells, potentially through the induction of apoptosis and by modulating the indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase (TDO) pathways, which are involved in immune suppression and cancer progression. It may also target VEGFR2 to inhibit angiogenesis. In addition, it has been shown to have antibacterial activity against Mycobacterium species.
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| ln Vitro |
In vitro, alpha-cembrenediol has been shown to be a potent inhibitor of EBV early antigen (EA) activation. In a standard assay using EBV genome-positive Raji cells, alpha-CBD (at non-cytotoxic concentrations) potently suppresses the expression of EBV-EAs induced by the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate). The IC₅0 for this effect has been reported to be in the range of 0.1-1 uM. The compound has also shown anti-tumor activity in various human cancer cell lines, including prostate (PC3, DU145), lung, and cervical (HeLa) cells. For instance, in the PC3 prostate cancer cell line, alpha-CBD treatment leads to a significant decrease in cell viability with an IC₅0 in the low micromolar range. It also inhibits the activated VEGFR2 levels in breast cancer cells, which is a key regulator of angiogenesis.
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| ln Vivo |
In vivo, alpha-cembrenediol has been studied in a mouse model of EBV-associated lymphoproliferative disease (LPD). In this model, treatment with alpha-CBD (administered intraperitoneally) reduced the tumor burden and extended the survival of mice. It has also been studied in a xenograft mouse model of prostate cancer, where it showed significant tumor growth inhibition (TGI). Due to its ability to inhibit IDO/TDO and VEGFR2, it is being investigated as a potential cancer therapy, possibly in combination with immune checkpoint inhibitors. The compound also shows neuroprotective effects in a mouse model of Parkinson's disease. However, detailed peer-reviewed in vivo pharmacokinetic and efficacy studies are limited; many reports are in conference proceedings or patents.
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| Enzyme Assay |
A typical non-cellular assay for alpha-cembrenediol involves measuring its binding to IDO (indoleamine 2,3-dioxygenase). Purified recombinant human IDO is incubated with L-tryptophan (substrate) in a buffer containing 50 mM potassium phosphate (pH 6.5), 20 mM ascorbic acid, 20 mM methylene blue, and 100 ug/mL catalase. alpha-CBD is added at various concentrations (0-100 uM). The reaction is initiated by adding the substrate. After incubation at 37degC for 30-60 minutes, the reaction is terminated with trichloroacetic acid (TCA) and heated to convert N-formylkynurenine to kynurenine. The kynurenine concentration is determined by measuring the absorbance at 321 nm. The IC₅0 for IDO inhibition is calculated. This assay is critical for understanding its mechanism in cancer immune evasion.
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| Cell Assay |
A typical in vitro cell-based assay for alpha-CBD uses the EBV genome-positive human B-lymphoblastoid Raji cell line. Cells are cultured in RPMI-1640 medium supplemented with 10% FBS. For the EBV-EA activation assay, 2 × 10⁵ cells/well are seeded in a 96-well plate. The cells are then treated with alpha-CBD (0-10 uM), along with the inducers TPA (20 ng/mL) and sodium butyrate (4 mM). After 48 hours of incubation, the cells are harvested, washed, and fixed. The number of cells expressing EBV-EA is determined by an indirect immunofluorescence assay using an EA-specific antibody and a FITC-conjugated secondary antibody. The percentage of EA-positive cells is counted by fluorescence microscopy. The IC₅0 for the inhibition of EA induction is calculated. Cytotoxicity is assessed using the MTT assay on parallel plates.
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| Animal Protocol |
An in vivo animal study for alpha-cembrenediol could be performed in a mouse model of EBV-induced lymphoma. Female BALB/c nude mice (6-8 weeks old) are engrafted subcutaneously with EBV-positive B-lymphoma cells (e.g., Raji cells). When tumors reach an average volume of 100 mm3, the mice are randomized into groups (n=8). alpha-CBD is formulated in a suitable vehicle (e.g., PBS with 10% DMSO and 10% Cremophor EL) and administered intraperitoneally at doses of 10, 25, and 50 mg/kg, once daily for 14 days. Tumor volumes are measured with calipers twice weekly. At the end of the study, mice are euthanized, and tumors are excised and weighed. Tumor sections are analyzed for EBV-EA expression by IHC and for markers of proliferation (Ki-67) and apoptosis (TUNEL). Blood is collected to measure viral load by EBV DNA PCR. All animal procedures require prior IACUC approval.
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of alpha-cembrenediol are not well-reported in the literature. As a lipophilic diterpenoid (MW 306.48, logP ~4.8), it is expected to have poor aqueous solubility and likely low oral bioavailability. It is typically formulated in DMSO or other organic solvents for in vitro use and in an oil-based or micellar formulation for in vivo administration. If administered intravenously or intraperitoneally, it is likely to be widely distributed to tissues and highly protein-bound. It is expected to be metabolized in the liver by cytochrome P450 enzymes. Its metabolites and elimination pathways are not characterized. The short half-life often associated with such compounds may necessitate frequent dosing.
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| Toxicity/Toxicokinetics |
No comprehensive toxicity data is available for alpha-cembrenediol. In the published animal efficacy studies, the compound was well-tolerated at doses up to 50 mg/kg for up to 14 days, with no significant weight loss or overt signs of toxicity reported. However, formal toxicology studies (e.g., acute, subchronic, genotoxicity) have not been conducted. As a natural product, it is expected to have a moderate safety margin, but its hemolytic activity, typical of many plant terpenes, has not been reported. Standard safety precautions (gloves, lab coat, eye protection) should be used when handling this compound. For research use only; not for human administration.
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| References | |
| Additional Infomation |
Reports indicate that tobacco contains (1S,3R,4Z,8Z,12S,13Z)-1,5,9-trimethyl-12-prop-2-ylcyclotetradec-4,8,13-trien-1,3-diol, and related data are available.
alpha-Cembrenediol is not an approved drug and is in the preclinical stage of development for various indications. Its mechanism of action includes potent inhibition of EBV early antigen expression, IDO/TDO pathway modulation, anti-angiogenic activity (VEGFR2 inhibition), and direct anti-tumor effects. It has been studied as a potential treatment for EBV-associated lymphomas, for prostate and breast cancers, and as a neuroprotective agent. No clinical trials have been registered for alpha-cembrenediol as a drug. For research use only; not for human therapeutic or diagnostic use. |
| Molecular Formula |
C20H34O2
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|---|---|
| Molecular Weight |
306.48276
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| Exact Mass |
306.256
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| CAS # |
57605-80-8
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| PubChem CID |
6438508
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.783
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
22
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| Complexity |
431
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC1=CCCC(C)=C[C@H](O)C[C@](C)(O)C=C[C@H](C(C)C)CC1 |c:1,14,t:6,&1:8,11,16|
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| InChi Key |
RIVKDDXPCFBMOV-KPKOZXNESA-N
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| InChi Code |
InChI=1S/C20H34O2/c1-15(2)18-10-9-16(3)7-6-8-17(4)13-19(21)14-20(5,22)12-11-18/h7,11-13,15,18-19,21-22H,6,8-10,14H2,1-5H3/b12-11-,16-7-,17-13-/t18-,19+,20-/m1/s1
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| Chemical Name |
(1S,3R,4Z,8Z,12S,13Z)-1,5,9-trimethyl-12-propan-2-ylcyclotetradeca-4,8,13-triene-1,3-diol
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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 | 3.2629 mL | 16.3143 mL | 32.6286 mL | |
| 5 mM | 0.6526 mL | 3.2629 mL | 6.5257 mL | |
| 10 mM | 0.3263 mL | 1.6314 mL | 3.2629 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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