| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
4-Deoxy-4alpha-phorbol itself does not have a specific, well-defined molecular target for its own biological activity, as it is primarily a synthetic intermediate. However, its derivatives, synthesized from it, target protein kinase C (PKC). PKC is a family of serine/threonine kinases that play critical roles in cell signaling, proliferation, and differentiation. Phorbol esters, such as PMA, are potent PKC activators by binding to the C1 domain. The goal of using 4-deoxy-4alpha-phorbol as a precursor is to create novel PKC modulators (both activators and inhibitors) with therapeutic potential, including the inhibition of HIV-1 replication. In the context of HIV-1, the ultimate target is the virus itself, specifically the mechanism by which it induces syncytia formation and cytopathic effects in T-cells.
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| ln Vitro |
The biological activity of 4-Deoxy-4alpha-phorbol is not directly reported; its activity is conferred by the phorbol esters synthesized from it. The parent compound itself has been evaluated and is considered inactive as a tumor promoter and has low PKC binding affinity. In vitro assays are used to characterize the PKC activity of its derivatives. For example, a derivative may be tested for its ability to inhibit HIV-1-induced cytopathic effects in MT-4 cells. In such assays, a derivative might show an EC₅0 (half-maximal effective concentration) in the low micromolar range. The compound can also be tested for its ability to bind to PKC in a competition assay using [3H]phorbol dibutyrate (PDBu) as a radioligand.
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| ln Vivo |
There are no reported in vivo studies for 4-Deoxy-4alpha-phorbol itself. Any in vivo activity would be associated with its semisynthetic derivatives. For an HIV-1 inhibitory phorbol derivative, in vivo efficacy could be assessed in an animal model of HIV-1, such as a humanized mouse model. In such studies, the test compound would be administered, and viral load would be measured, along with CD4+ T-cell counts, to evaluate its ability to control viral replication. However, due to the known tumor-promoting activity of many phorbols, a major focus of in vivo studies would be to evaluate any potential carcinogenic or pro-inflammatory activity of the new derivatives, which is not applicable to 4-deoxy-4alpha-phorbol itself.
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| Enzyme Assay |
A typical non-cellular PKC binding assay for a phorbol derivative uses a competitive binding format. The assay buffer is 20 mM Tris-HCl (pH 7.5), 0.5 mM CaCl2, 100 ug/mL phosphatidylserine (PS). A mixture of 20 nM [3H]phorbol-12,13-dibutyrate (PDBu) (the tracer) and varying concentrations (0-100 uM) of the test compound are incubated with 100 nM of purified PKC (alpha, beta, or gamma isozyme) in a 96-well plate at 25degC for 2 hours. Non-specific binding is determined with 1 uM unlabeled PDBu. The reaction is terminated by rapid filtration through GF/B filters, and the retained radioactivity is measured by scintillation counting. The IC₅0 for the test compound is calculated.
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| Cell Assay |
A standard in vitro cell-based assay for a phorbol derivative is a cytotoxicity assay against HIV-1-infected cells. Human MT-4 T-cells are cultured in RPMI-1640 medium with 10% FBS. The cells are infected with HIV-1 (e.g., IIIB strain) at a multiplicity of infection (MOI) of 0.01. Following infection, 2 × 10⁴ cells are plated per well in a 96-well plate. Serial dilutions of the test compound (0.1-100 uM) are added. After 5 days of incubation at 37degC, cell viability is measured using the MTT assay. The concentration of the compound that inhibits 50% of the virus-induced cytopathic effect (EC₅0) is calculated. A parallel assay is run with uninfected cells to evaluate the compound's own cytotoxicity (CC₅0). The selectivity index (SI = CC₅0/EC₅0) is then calculated.
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| Animal Protocol |
There is no standard animal study protocol for 4-Deoxy-4alpha-phorbol itself as it is a synthetic intermediate. However, for an HIV-1 inhibitory derivative, the in vivo efficacy might be assessed in a xenograft model. For instance, NOD/SCID/gammac(null) (NSG) mice could be engrafted with human peripheral blood mononuclear cells (PBMCs) and subsequently infected with HIV-1. After infection, mice could be treated intraperitoneally with the test compound daily for 14-28 days. Viral loads in plasma would be measured by qRT-PCR. The number of CD4+ T-cells in peripheral blood would be monitored by flow cytometry. At the end of the study, spleen and lymph nodes would be analyzed for viral RNA and proviral DNA. However, this is hypothetical for 4-deoxy-4alpha-phorbol.
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| ADME/Pharmacokinetics |
The pharmacokinetic (PK) properties of 4-Deoxy-4alpha-phorbol are not reported. As a small, lipophilic diterpene (MW ~348.43, logP ~3.0), it is expected to be well-absorbed orally, but this is not documented. Its metabolism would likely involve hepatic phase I (oxidation) and phase II (conjugation) reactions. Given its structural similarity to phorbol, it may have moderate to high clearance. No human or detailed animal PK data is publicly available. The compound is used solely for in vitro research and as an intermediate, so its in vivo PK is not a focus of study.
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| Toxicity/Toxicokinetics |
No toxicity data is available for 4-Deoxy-4alpha-phorbol as a standalone compound. As a research chemical, it should be handled with caution using standard safety precautions. The major safety concern associated with its structural class is tumor promotion. Phorbol esters are potent activators of PKC and are powerful tumor promoters. While 4-deoxy-4alpha-phorbol itself is non-tumorigenic, its derivatives could be highly toxic. Therefore, laboratories should handle it as a potential carcinogen, and gloves and lab coats should be worn at all times to prevent skin contact. Its MSDS advises that it is for research use only.
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| References | |
| Additional Infomation |
See also: 4-deoxy-4α-phorbolol (note moved to).
4-Deoxy-4alpha-phorbol is not a drug and has no clinical status. It is a research chemical that serves as a natural product scaffold for the semisynthesis of novel phorbol ester analogs. Its primary scientific value is as a precursor for creating compounds that modulate PKC activity, with a historical focus on discovering new treatments for HIV-1. Research on these compounds has waned due to the success of modern antiretroviral therapies (ART), but the scaffold remains a tool for studying PKC signaling. No clinical trials have been registered for 4-deoxy-4alpha-phorbol or its derivatives. For research use only; not for human therapeutic applications. |
| Molecular Formula |
C20H28O5
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|---|---|
| Molecular Weight |
348.43
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| Exact Mass |
348.194
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| CAS # |
37415-57-9
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| PubChem CID |
500452
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| Appearance |
White to off-white solid powder
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| LogP |
0.815
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
25
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| Complexity |
707
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| Defined Atom Stereocenter Count |
8
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| SMILES |
C[C@@H]1[C@H]([C@@]2([C@@H](C2(C)C)[C@H]3[C@]1([C@@H]4C=C(C(=O)[C@@H]4CC(=C3)CO)C)O)O)O
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| InChi Key |
RTJAYUGZUOLFMY-YLKPGCRESA-N
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| InChi Code |
InChI=1S/C20H28O5/c1-9-5-13-12(15(9)22)6-11(8-21)7-14-16-18(3,4)20(16,25)17(23)10(2)19(13,14)24/h5,7,10,12-14,16-17,21,23-25H,6,8H2,1-4H3/t10-,12-,13-,14+,16-,17-,19+,20-/m1/s1
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| Chemical Name |
(1R,2R,6R,10S,11R,13S,14R,15R)-1,13,14-trihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyltetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dien-5-one
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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 | 2.8700 mL | 14.3501 mL | 28.7002 mL | |
| 5 mM | 0.5740 mL | 2.8700 mL | 5.7400 mL | |
| 10 mM | 0.2870 mL | 1.4350 mL | 2.8700 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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