| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Phorbol-12,13-didecanoate targets protein kinase C (PKC) family isozymes by binding to the C1 domain, similar to the endogenous activator diacylglycerol (DAG). This binding leads to PKC activation and subsequent downstream signaling cascades. Additionally, the compound is an agonist of the transient receptor potential vanilloid 4 (TRPV4) channel, which may be independent of PKC activation.
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| ln Vitro |
Phorbol-12,13-didecanoate exhibits potent in vitro activity as a PKC activator, with efficacy comparable to that of PMA. It demonstrates significant antiviral activity, inhibiting chikungunya virus (CHIKV) replication with an EC50 of 6.0 +/- 0.9 nM and a high selectivity index. It also shows anti-HIV activity, with EC50 values of 1.2 nM (HIV-1) and 0.2 nM (HIV-2) in MT4 cells. The compound causes rapid and reversible inhibition of electrical cell coupling in culture and induces changes in actin-containing structures. It is a strong NO promoter and promotes iNOS expression in cultured hepatocytes. PDD significantly alters the growth properties of early passage normal human skin cells in vitro.
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| ln Vivo |
In vivo, Phorbol-12,13-didecanoate acts as a potent tumor promoter in two-stage skin carcinogenesis models. It stimulates angiogenesis in a dose-dependent manner in chick chorioallantoic membrane and rabbit cornea assays, a property closely correlated with its tumor-promoting activity. The active tumor promoters TPA and PDD, which activate PKC, were found to stimulate angiogenesis, whereas 4alpha-phorbol 12,13-didecanoate (the inactive stereoisomer) did not. PDD also induces inflammatory responses and has been shown to cause secretory responses in porcine jejunum in vivo.
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| Enzyme Assay |
The in vitro potency of PKC activation by phorbol esters is typically measured using a [gamma-32P]ATP-based kinase activity assay. PKC enzyme is incubated with PDD (0.1 nM-10 uM) and phospholipids (e.g., phosphatidylserine) in the presence of a PKC substrate peptide. The reaction is terminated, and incorporated radioactivity is measured. For binding studies, [3H]phorbol 12,13-dibutyrate (PDBu) displacement assays using rat brain synaptosomes or recombinant PKC are employed. PDD is also used in cell-based PKC translocation assays. The inactive stereoisomer 4alpha-phorbol 12,13-didecanoate (4alpha-PDD) is often used as a negative control, as it binds but does not activate PKC.
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| Cell Assay |
For cell-based assays, cells (e.g., Vero, MT4, fibroblasts) are cultured in multi-well plates and treated with Phorbol-12,13-didecanoate at concentrations ranging from 1 nM to 10 uM for various time points. Antiviral activity is assessed by measuring virus-induced cytopathic effect or cell viability via MTT assay after 5-7 days of infection. Activation of PKC is measured by immunofluorescence detection of PKC translocation from the cytosol to the membrane, or by Western blotting for downstream phosphorylation targets such as ERK1/2 or MARCKS. Inhibition of human skin fibroblast proliferation by PDD is mediated by PKC, with the beta-isomer having an IC50 of less than 0.1 nM, while the alpha-isomer is inactive.
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| Animal Protocol |
In vivo tumor promotion protocols for Phorbol-12,13-didecanoate are well-established in two-stage skin carcinogenesis models. Female CD-1 mice (6-7 weeks old) are shaved on the dorsal skin and initiated with a sub-carcinogenic dose of DMBA (100-200 ug in acetone, single topical dose). One week later, promotion is performed by topical application of PDD (2.5-10 ug, typically twice weekly for 20-30 weeks). Tumors are counted weekly and confirmed by histopathology. For angiogenesis studies, the chick chorioallantoic membrane (CAM) assay is used, with PDD applied directly to the CAM and vascularization assessed after 72 hours. Both TPA and PDD at concentrations as low as 10-7 M are tumor promoting.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for Phorbol-12,13-didecanoate is limited, but studies indicate that its metabolism varies across species. Unlike TPA, PDD is degraded much more slowly in rodent fibroblasts and human hepatoma cells, with a half-life extending over days rather than hours. The major metabolite produced is phorbol-12-decanoate, which is virtually inactive, and phorbol-13-decanoate, which is 17-40 times less active than PDD. As a highly lipophilic compound (LogP ≈ 7.3), it readily crosses cell membranes and is expected to have significant tissue distribution and skin permeability.
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| Toxicity/Toxicokinetics |
Phorbol-12,13-didecanoate is classified as a potent skin irritant, tumor promoter, and suspected carcinogen. According to safety data sheets, it is acutely toxic, with hazard statements H300 (Fatal if swallowed), H310 (Fatal in contact with skin), and H330 (Fatal if inhaled). It may cause allergy or asthma symptoms or breathing difficulties if inhaled (H334) and is suspected of causing cancer (H351). The inactive stereoisomer 4alpha-phorbol 12,13-didecanoate (4alpha-PDD) is non-tumor-promoting and does not activate PKC. Extreme caution and appropriate personal protective equipment are required when handling this compound.
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| References |
[1]. Enomoto T, et al. Tumor promoters cause a rapid and reversible inhibition of the formation and maintenance of electrical cell coupling in culture. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5628-32.
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| Additional Infomation |
Phorbol-12,13-didecanoate is a protein kinase C (PKC) activator and tumor promoter that binds to the C1 domain of PKC with high affinity, mimicking the action of diacylglycerol (DAG). It is more potent than PMA as an inflammatory agent but weaker as a tumor promoter. The compound is also an activator of TRPV4 channels, with the inactive stereoisomer 4alpha-PDD being a selective TRPV4 agonist. Its antiviral activity is likely mediated through PKC activation, which interferes with viral replication. Phorbol-12,13-didecanoate is not approved for clinical use. The product is for research use only.
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| Molecular Formula |
C40H64O8
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| Molecular Weight |
672.93
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| Exact Mass |
672.46
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| CAS # |
24928-17-4
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| PubChem CID |
452543
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.14g/cm3
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| Boiling Point |
734.2ºC at 760 mmHg
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| Flash Point |
212.4ºC
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| Vapour Pressure |
6.92E-25mmHg at 25°C
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| Index of Refraction |
1.546
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| LogP |
7.313
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
21
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| Heavy Atom Count |
48
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| Complexity |
1220
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| Defined Atom Stereocenter Count |
8
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| SMILES |
CCCCCCCCCC(OC1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(=CC2C2C(C)(C)C12OC(CCCCCCCCC)=O)CO)=O
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| InChi Key |
DGOSGFYDFDYMCW-MWRBZVGOSA-N
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| InChi Code |
InChI=1S/C40H64O8/c1-7-9-11-13-15-17-19-21-32(42)47-36-28(4)39(46)30(24-29(26-41)25-38(45)31(39)23-27(3)35(38)44)34-37(5,6)40(34,36)48-33(43)22-20-18-16-14-12-10-8-2/h23-24,28,30-31,34,36,41,45-46H,7-22,25-26H2,1-6H3/t28-,30+,31-,34-,36-,38-,39-,40-/m1/s1
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| Chemical Name |
[(1S,2S,6R,10S,11R,13S,14R,15R)-13-decanoyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] decanoate
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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 | 1.4860 mL | 7.4302 mL | 14.8604 mL | |
| 5 mM | 0.2972 mL | 1.4860 mL | 2.9721 mL | |
| 10 mM | 0.1486 mL | 0.7430 mL | 1.4860 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.
Products are for research use only; We do not sell to patients
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