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| Targets |
Tripterifordin is recognized as an anti-HIV agent that targets HIV protease, an essential enzyme for viral replication. HIV protease is responsible for cleaving viral polyprotein precursors into functional proteins required for the assembly and maturation of infectious viral particles. By inhibiting this enzyme, Tripterifordin prevents the production of mature, infectious HIV virions. The compound exhibits significant anti-HIV replication activity in H9 lymphocyte cells, with an EC₅₀ value of 3,100 nM (approximately 1 µg/mL). This antiviral activity suggests that Tripterifordin interferes with critical steps in the HIV life cycle, likely through direct interaction with the viral protease active site or through allosteric modulation of protease function. Beyond its antiviral target, Tripterifordin has also shown cytotoxic and immunosuppressive activities, indicating that it may interact with cellular targets involved in cell proliferation and immune regulation. In human A2780 ovarian cancer cells, Tripterifordin exhibits cytotoxicity with an IC₅₀ greater than 60 µM. In human HMy2.C1R cells, it demonstrates immunosuppressive activity with an IC₅₀ of 56.3 µM, as assessed by cell growth inhibition after 48 hours using a sulforhodamine B (SRB) assay. These findings suggest that Tripterifordin may have multiple molecular targets, contributing to its diverse biological activities.
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| ln Vitro |
In vitro studies have demonstrated that Tripterifordin possesses significant anti-HIV replication activity in H9 lymphocyte cells, a human T-cell line commonly used for HIV research. The compound shows an EC₅₀ value of 3,100 nM (approximately 1 µg/mL) against HIV replication in these cells, indicating potent antiviral efficacy. This activity is measured by assessing the inhibition of viral replication through various endpoints, including the reduction of p24 antigen production or viral RNA levels in infected cell cultures. In addition to its antiviral effects, Tripterifordin exhibits cytotoxicity against human A2780 ovarian cancer cells, with an IC₅₀ greater than 60 µM, indicating relatively low cytotoxicity in this cell line at concentrations that are effective against HIV. The compound also demonstrates immunosuppressive activity in human HMy2.C1R cells, with an IC₅₀ of 56.3 µM, as assessed by cell growth inhibition measured after 48 hours using the SRB assay. This immunosuppressive activity suggests that Tripterifordin may modulate immune cell function, potentially through effects on cell signaling pathways or gene expression. The compound's ability to inhibit HIV replication while exhibiting relatively low cytotoxicity in certain cell types makes it an attractive candidate for further development as an antiviral agent. However, its immunosuppressive effects warrant careful consideration, as they could potentially limit its therapeutic utility or contribute to beneficial immunomodulatory effects in certain disease contexts.
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| ln Vivo |
Detailed in vivo activity data for Tripterifordin are limited in the available literature. Most of the biological characterization of this compound has been conducted in vitro, using cell-based assays to evaluate its antiviral, cytotoxic, and immunosuppressive activities. The potent anti-HIV activity observed in H9 lymphocyte cells suggests that Tripterifordin has the potential for in vivo efficacy, but comprehensive animal studies are needed to confirm this and to establish its pharmacokinetic and pharmacodynamic profiles. As an HIV inhibitor, Tripterifordin could potentially be studied in humanized mouse models or in simian immunodeficiency virus (SIV)-infected macaques to evaluate its antiviral efficacy, pharmacokinetics, and safety profile in a living system. These animal models are standard for preclinical evaluation of anti-HIV candidates and would provide critical information on the compound's absorption, distribution, metabolism, and excretion, as well as its ability to reduce viral load and prevent disease progression. The lack of published in vivo data highlights the need for further research to advance Tripterifordin from a promising in vitro hit to a viable preclinical candidate. Such studies would be essential for determining the compound's therapeutic potential and for guiding the design of future clinical trials.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for HIV protease inhibitors like Tripterifordin typically involve measuring the inhibition of recombinant HIV protease activity using fluorogenic or chromogenic peptide substrates. The assay is conducted by incubating purified HIV protease enzyme with varying concentrations of the test compound in the presence of a suitable substrate that mimics the natural cleavage site of the viral polyprotein. Upon cleavage by the protease, the substrate releases a fluorophore or chromophore that can be quantified using a fluorescence or absorbance plate reader. The inhibitory activity of Tripterifordin is determined by calculating the IC₅₀ value, which represents the concentration required to inhibit 50% of the enzyme activity. For binding affinity studies, surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) can be used to measure the direct interaction between Tripterifordin and HIV protease, providing information on the binding kinetics and thermodynamics. These assays are essential for confirming the mechanism of action of Tripterifordin as an HIV protease inhibitor and for guiding structure-activity relationship studies to optimize its potency and selectivity.
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| Cell Assay |
In vitro cell-based assays for Tripterifordin are primarily conducted using H9 lymphocyte cells infected with HIV to evaluate its antiviral activity. The assay involves infecting H9 cells with a laboratory-adapted strain of HIV and then treating the infected cells with serial dilutions of Tripterifordin. After a defined incubation period (typically 3-7 days), the extent of viral replication is quantified by measuring the levels of HIV p24 antigen in the culture supernatant using ELISA, or by measuring viral RNA levels using RT-PCR. The EC₅₀ value is calculated as the concentration of the compound that reduces viral replication by 50% compared to untreated infected controls. Cytotoxicity is assessed in parallel using uninfected cells to determine the CC₅₀ value, and the selectivity index (SI = CC₅₀/EC₅₀) is calculated to evaluate the compound's therapeutic window. In human A2780 ovarian cancer cells, cytotoxicity is assessed by measuring cell viability after 48 hours of treatment using the MTT assay. In human HMy2.C1R cells, immunosuppressive activity is evaluated by measuring cell growth inhibition after 48 hours using the SRB assay. These cell-based assays provide critical information on the compound's antiviral efficacy, cytotoxicity, and potential immunomodulatory effects, which are essential for assessing its suitability for further development.
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| Animal Protocol |
In vivo animal model data for Tripterifordin are not well-documented in the available literature. The compound has not been extensively studied in animal models, and comprehensive pharmacokinetic, pharmacodynamic, and toxicological studies are lacking. As an HIV inhibitor with potent in vitro activity, Tripterifordin would typically be evaluated in animal models such as humanized mice (mice engrafted with human hematopoietic stem cells that support HIV infection) or in non-human primates infected with SIV. These models would allow researchers to assess the compound's ability to reduce viral load, its pharmacokinetic properties (absorption, distribution, metabolism, and excretion), and its safety profile in a living system. Standard in vivo protocols for evaluating anti-HIV candidates typically involve oral or intravenous administration of the test compound, followed by monitoring of viral load, CD4+ T-cell counts, and clinical parameters over several weeks. Pharmacokinetic studies would involve collecting blood and tissue samples at various time points to determine the compound's half-life, bioavailability, and tissue distribution. Until such studies are conducted, the in vivo efficacy and safety of Tripterifordin remain largely unknown.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) data for Tripterifordin are currently limited, as the compound is primarily a research tool and has not undergone extensive preclinical or clinical development. No published studies have systematically characterized its absorption, distribution, metabolism, and excretion (ADME) properties. Given its diterpene lactone structure and relatively low molecular weight (318.45 g/mol), Tripterifordin is likely to have moderate lipophilicity, which could influence its oral bioavailability and tissue distribution. As a natural product isolated from plant sources, it may be subject to extensive first-pass metabolism in the liver, potentially limiting its oral bioavailability. The compound's stability in biological fluids and its potential for protein binding are also unknown. For HIV protease inhibitors, achieving adequate plasma concentrations and tissue penetration is critical for efficacy, and Tripterifordin would need to demonstrate favorable PK properties to be considered a viable drug candidate. The lack of PK data underscores the need for comprehensive ADME studies to advance Tripterifordin toward preclinical development.
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| Toxicity/Toxicokinetics |
Toxicity data for Tripterifordin are limited, with available information primarily derived from in vitro cytotoxicity assays. In human A2780 ovarian cancer cells, Tripterifordin shows an IC₅₀ greater than 60 µM, indicating relatively low cytotoxicity in this cell line at concentrations that are effective against HIV replication. In human HMy2.C1R cells, the compound exhibits immunosuppressive activity with an IC₅₀ of 56.3 µM, suggesting that it may modulate immune cell function at higher concentrations. These in vitro cytotoxicity data provide some insight into the compound's safety profile, but comprehensive toxicological studies are lacking. No data are available on acute or chronic toxicity in animal models, genotoxicity, carcinogenicity, or reproductive toxicity. The compound's natural product origin from Tripterygium wilfordii, a plant known to contain other bioactive and potentially toxic constituents, warrants caution. Tripterygium wilfordii extracts have been associated with various toxicities, including hepatotoxicity, nephrotoxicity, and reproductive toxicity, although Tripterifordin itself may have a more favorable safety profile. Thorough toxicological evaluation would be necessary before Tripterifordin could be considered for clinical development.
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| References | |
| Additional Infomation |
Reports indicate that Tripterygium wilfordii and Gynocardia odorata contain tripterycin, and relevant data is available for reference.
Tripterifordin is a novel and potent anti-AIDS agent isolated from the roots of Tripterygium wilfordii Hook. f. It has significant anti-HIV replication activity in H9 lymphocyte cells, with an EC₅₀ value of 3,100 nM (approximately 1 µg/mL). The compound also exhibits cytotoxicity against human A2780 cells (IC₅₀ >60 µM) and immunosuppressive activity in human HMy2.C1R cells (IC₅₀ 56.3 µM). As a kaurane-type diterpene lactone, Tripterifordin represents an interesting scaffold for medicinal chemistry optimization. Its mechanism of action as an HIV protease inhibitor makes it a valuable tool for studying viral replication and for developing new antiviral strategies. However, the compound has not yet progressed to clinical trials or received regulatory approval for any indication. It remains primarily a research tool for drug discovery, used to investigate HIV biology and to explore the potential of natural products as sources of new antiviral agents. Further research is needed to fully characterize its pharmacological profile, including its in vivo efficacy, pharmacokinetics, and safety, before it can be considered for clinical development. |
| Molecular Formula |
C20H30O3
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|---|---|
| Molecular Weight |
318.4504
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| Exact Mass |
318.219
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| CAS # |
139122-81-9
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| PubChem CID |
72369
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
485.1±45.0 °C at 760 mmHg
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| Flash Point |
198.6±21.5 °C
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| Vapour Pressure |
0.0±2.8 mmHg at 25°C
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| Index of Refraction |
1.570
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
23
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| Complexity |
573
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| Defined Atom Stereocenter Count |
7
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| SMILES |
O1C(C2(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])[C@]3(C1([H])[H])[C@]2([H])C([H])([H])C([H])([H])[C@]12C([H])([H])[C@](C([H])([H])[H])([C@]([H])(C([H])([H])C([H])([H])C13[H])C2([H])[H])O[H])=O
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| InChi Key |
KLMZPLYXGZZBCX-CJSYXLNHSA-N
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| InChi Code |
InChI=1S/C20H30O3/c1-17-7-3-8-20(12-23-16(17)21)14(17)6-9-19-10-13(4-5-15(19)20)18(2,22)11-19/h13-15,22H,3-12H2,1-2H3/t13-,14-,15-,17-,18-,19+,20+/m1/s1
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| Chemical Name |
(1R,2R,5R,6R,8S,11S,12R)-6-hydroxy-6,12-dimethyl-14-oxapentacyclo[10.3.3.15,8.01,11.02,8]nonadecan-13-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 | 3.1402 mL | 15.7011 mL | 31.4021 mL | |
| 5 mM | 0.6280 mL | 3.1402 mL | 6.2804 mL | |
| 10 mM | 0.3140 mL | 1.5701 mL | 3.1402 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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