| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Triptolide palmitate targets multiple cellular pathways, primarily through the action of its parent compound, triptolide. Triptolide is known to inhibit the transcription factor NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells) and heat shock protein 70 (HSP70). It also activates caspases, leading to apoptosis. Triptolide palmitate, as a prodrug, is likely hydrolyzed in vivo to release triptolide, which then exerts its effects. Triptolide has also been shown to inhibit X-linked inhibitor of apoptosis protein (XIAP) and other anti-apoptotic proteins. The palmitate esterification improves the lipophilicity of triptolide, enhancing its ability to be encapsulated in lipid-based drug delivery systems (e.g., liposomes, lipid nanoparticles) and improving its pharmacokinetic profile. The molecular target of the palmitate moiety itself is not biologically active; it is purely a chemical modification to improve drug delivery.
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| ln Vitro |
The in vitro activity of triptolide palmitate is characterized by its cytotoxicity against cancer cell lines. Studies have shown that triptolide palmitate exhibits potent cytotoxicity against MCF-7 human breast cancer cells and A549 human lung cancer cells, with IC50 values of 7.5 uM and 6.4 uM, respectively. This cytotoxic activity is comparable to that of unmodified triptolide, indicating that the palmitate esterification does not abolish the anti-cancer activity. The compound is also significantly more potent against cancer cells than against normal cells, suggesting a degree of selectivity. In addition to cytotoxicity, triptolide palmitate induces apoptosis in cancer cells, as evidenced by increased caspase-3/7 activity, PARP cleavage, and annexin V staining. The palmitate modification may also allow for the incorporation of triptolide palmitate into lipid-based nanoparticles for improved delivery.
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| ln Vivo |
The in vivo activity of triptolide palmitate has been evaluated in animal models, with a focus on its improved pharmacokinetics and antitumor efficacy compared to triptolide. In Sprague Dawley rats, the plasma half-life (t½) of triptolide palmitate was determined to be 50.4 minutes. This represents a significant improvement over unmodified triptolide, which has a very short half-life (approximately 5-10 minutes in rodents). The improved half-life allows for more sustained drug exposure and potentially enhanced antitumor efficacy. In a xenograft mouse model of lung cancer, treatment with triptolide palmitate formulated in lipid nanoparticles resulted in greater tumor growth inhibition compared to free triptolide, with reduced systemic toxicity. The compound also showed improved biodistribution to tumor tissues, likely due to the enhanced permeability and retention (EPR) effect.
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| Enzyme Assay |
As a prodrug, triptolide palmitate does not have a direct enzyme binding site; it is designed to be metabolized to the active parent compound, triptolide. Therefore, a cell-free assay for triptolide palmitate typically measures the rate of hydrolysis to triptolide and palmitic acid. A standard protocol: (1) Prepare a 1 mM stock solution of triptolide palmitate in DMSO. (2) Dilute the compound to 10 uM in various biological matrices: PBS (pH 7.4), human plasma, rat plasma, and liver microsome solution (0.5 mg/mL microsomal protein in 100 mM phosphate buffer, pH 7.4, containing 1 mM NADPH to simulate metabolism). (3) Incubate at 37degC in a water bath with gentle shaking. (4) At various time points (0, 5, 10, 15, 30, 60, 90, 120 minutes), remove an aliquot (50-100 uL) and immediately add 3 volumes of ice-cold acetonitrile containing an internal standard to stop the reaction and precipitate proteins. (5) Centrifuge at 13,000 rpm for 10 minutes. (6) Analyze the supernatant by LC-MS/MS, monitoring both triptolide palmitate (parent compound) and triptolide (the hydrolysis product). (7) Calculate the percentage of parent compound remaining and the amount of triptolide formed. (8) Determine the hydrolysis half-life (t½) by fitting the disappearance of the parent compound to a one-phase exponential decay model. (9) For enzyme inhibition assays of triptolide (the active metabolite), standard protocols for NF-kappaB inhibition or HSP70 inhibition can be used, but these are not direct assays for the palmitate prodrug.
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| Cell Assay |
A standard cellular protocol for evaluating the cytotoxic activity of triptolide palmitate: (1) Culture MCF-7 human breast cancer cells in DMEM (or RPMI-1640) supplemented with 10% FBS and 1% penicillin-streptomycin at 37degC in 5% CO2. (2) Seed cells into 96-well plates at a density of 5,000-10,000 cells per well in 100 uL of medium and incubate overnight for attachment. (3) Prepare a 10 mM stock solution of triptolide palmitate in DMSO. (4) Dilute the stock in culture medium to final concentrations ranging from 0.1 uM to 100 uM (2-fold or 3-fold serial dilutions). The final DMSO concentration should be ≤0.5% in all wells. (5) Treat cells for 48 or 72 hours at 37degC. (6) For MTT assay: add 20 uL of 5 mg/mL MTT solution to each well and incubate for 4 hours. (7) Remove the medium and add 150 uL of DMSO to dissolve the formazan crystals. (8) Measure absorbance at 570 nm (with background subtraction at 650 nm) using a microplate reader. (9) Calculate cell viability as (OD570 of treated well)/(OD570 of control well) × 100%. (10) Determine the IC50 by plotting viability (%) vs. log concentration and fitting a sigmoidal dose-response curve (four-parameter logistic model). (11) For apoptosis detection, treat cells with the compound at 5-20 uM for 24-48 hours, then stain with FITC-annexin V and propidium iodide (PI) and analyze by flow cytometry. (12) For Western blotting, treat cells for 24 hours, lyse in RIPA buffer, and probe with antibodies against cleaved PARP, cleaved caspase-3, and XIAP.
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| Animal Protocol |
A standard in vivo protocol for evaluating the antitumor efficacy of triptolide palmitate in a lung cancer xenograft model: (1) Culture A549 human lung cancer cells (or other appropriate cancer cells). (2) Harvest cells, wash twice with PBS, and resuspend in serum-free medium or PBS at 1×10⁷ cells/mL. (3) Inject 5×10⁶ A549 cells subcutaneously into the right flank of 6-8 week old female BALB/c nude mice. (4) Monitor tumor growth with calipers until the average tumor volume reaches approximately 100-150 mm3 (typically 7-14 days). (5) Randomize mice into treatment groups (n=6-10 per group): (a) vehicle control; (b) triptolide palmitate (low dose, e.g., 1 mg/kg); (c) triptolide palmitate (high dose, e.g., 5 mg/kg); (d) free triptolide (positive control, 0.2 mg/kg, but adjust for tolerability). (6) Formulate triptolide palmitate in a suitable vehicle. For in vivo use, the compound can be dissolved in a co-solvent system: 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline. Alternatively, it can be incorporated into lipid nanoparticles or liposomes to improve solubility and pharmacokinetics. (7) Administer the formulations by intraperitoneal (IP) injection every day or every other day for 2-4 weeks. (8) Measure tumor volumes twice weekly using calipers, and calculate volume using the formula V = (length × width2)/2. (9) Record body weights twice weekly to monitor toxicity. (10) At the end of the treatment period (e.g., day 21 or 28), euthanize mice by CO2 asphyxiation. (11) Excise tumors, weigh them, and photograph them. (12) Fix a portion of the tumor in 10% neutral buffered formalin for histology (H&E staining, IHC for Ki-67 proliferation index, and TUNEL staining for apoptosis). (13) Snap-freeze the remaining tumor tissue in liquid nitrogen for Western blotting (cleaved caspase-3, cleaved PARP, XIAP) and for measuring triptolide concentrations (by LC-MS/MS) to confirm target engagement. (14) Collect blood by cardiac puncture for pharmacokinetic analysis (triptolide palmitate and triptolide levels) and for measuring serum markers of hepatotoxicity (ALT, AST) and kidney function (creatinine).
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| ADME/Pharmacokinetics |
The pharmacokinetic profile of triptolide palmitate was studied in Sprague Dawley rats: (1) Use male Sprague Dawley rats (200-250 g, n=3-5 per group). (2) Formulate triptolide palmitate in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline, or as a lipid-based formulation). (3) Administer a single intravenous (IV) dose of 2 mg/kg via the tail vein. (4) Collect blood samples (approximately 200-300 uL) from the jugular vein or by serial tail vein collection at the following time points: pre-dose (0), 2, 5, 10, 15, 30, 45, 60, 90, 120 minutes, and 3, 4, 6, 8, 12, and 24 hours post-dose. (5) Collect blood into heparinized tubes and immediately centrifuge at 3000×g for 10 minutes at 4degC to obtain plasma. (6) Store plasma at -80degC until analysis. (7) For analysis, add 3 volumes of ice-cold acetonitrile containing an internal standard (e.g., triptolide-d3 or a structurally related compound) to 50-100 uL of plasma to precipitate proteins. (8) Centrifuge at 13,000 rpm for 10 minutes. (9) Analyze the supernatant by LC-MS/MS using a C18 column and a mobile phase consisting of water and acetonitrile (both containing 0.1% formic acid). (10) Monitor the mass transitions for triptolide palmitate (parent ion → product ion) and triptolide. (11) Calculate pharmacokinetic parameters (AUC, Cmax, t½, CL, Vd) using non-compartmental analysis (Phoenix WinNonlin or similar software). (12) The reported half-life (t½) of triptolide palmitate in rats is 50.4 minutes.
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| Toxicity/Toxicokinetics |
The toxicological profile of triptolide palmitate is expected to be similar to that of the parent compound, triptolide, but with potentially reduced systemic toxicity due to improved pharmacokinetics and targeted delivery. Triptolide is known to cause significant hepatotoxicity (liver damage) and nephrotoxicity (kidney damage), along with gastrointestinal toxicity (nausea, vomiting, diarrhea), and testicular toxicity at high doses. Triptolide is also teratogenic. The therapeutic index (the ratio between toxic and effective doses) is very narrow for triptolide. The palmitate prodrug and lipid nanoparticle formulation are designed to improve the therapeutic index by reducing non-specific distribution to healthy tissues (particularly the liver) and increasing accumulation in tumor tissues via the EPR effect. In preclinical studies, triptolide palmitate formulated in nanoparticles showed reduced hepatotoxicity (lower serum ALT and AST levels) and better tolerability than free triptolide, while maintaining or improving antitumor efficacy. No formal studies have been published on the carcinogenicity, genotoxicity, or reproductive toxicity of triptolide palmitate. Standard safety precautions for handling cytotoxic compounds should be followed.
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| References | |
| Additional Infomation |
Triptolide palmitate (CAS 2126920-51-0) is a palmitate ester prodrug of triptolide, a bioactive diterpene triepoxide isolated from Tripterygium wilfordii (thunder god vine). Triptolide has potent anti-inflammatory, immunosuppressive, and anti-cancer activities, but its clinical development has been limited by poor water solubility, high systemic toxicity (especially hepatotoxicity), and a narrow therapeutic window. The palmitate ester increases lipophilicity, allowing triptolide palmitate to be incorporated into lipid-based drug delivery systems such as liposomes and lipid nanoparticles, which can improve pharmacokinetics and tumor targeting via the EPR effect. In a Sprague Dawley rat model, triptolide palmitate has a half-life of 50.4 minutes, a significant improvement over the short half-life of triptolide (5-10 minutes). Triptolide palmitate exhibits cytotoxicity against MCF-7 and A549 cancer cells (IC50 values 7.5 uM and 6.4 uM, respectively). The compound is for research use only and is not an FDA-approved drug. No clinical trials have been reported.
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| Molecular Formula |
C36H54O7
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|---|---|
| Molecular Weight |
598.81
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| Exact Mass |
598.387
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| CAS # |
2126920-51-0
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| PubChem CID |
171714238
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| Appearance |
ointment
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| Hydrogen Bond Donor Count |
0
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
43
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| Complexity |
1150
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| Defined Atom Stereocenter Count |
9
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| SMILES |
CCCCCCCCCCCCCCCC(=O)O[C@H]1[C@@]23[C@@H](O2)C[C@H]4C5=C(CC[C@@]4([C@]36[C@@H](O6)[C@H]7[C@@]1(O7)C(C)C)C)C(=O)OC5
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| InChi Key |
IQUZWSRBSSSQQN-JMZYWKSWSA-N
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| InChi Code |
InChI=1S/C36H54O7/c1-5-6-7-8-9-10-11-12-13-14-15-16-17-18-28(37)40-32-34(23(2)3)29(42-34)30-36(43-30)33(4)20-19-24-25(22-39-31(24)38)26(33)21-27-35(32,36)41-27/h23,26-27,29-30,32H,5-22H2,1-4H3/t26-,27-,29-,30-,32+,33-,34-,35+,36+/m0/s1
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| Chemical Name |
[(1S,2S,4S,5S,7S,8R,9R,11S,13S)-1-methyl-17-oxo-7-propan-2-yl-3,6,10,16-tetraoxaheptacyclo[11.7.0.02,4.02,9.05,7.09,11.014,18]icos-14(18)-en-8-yl] hexadecanoate
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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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ~100 mg/mL (~167.00 mM; with ultrasonication)
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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 | 1.6700 mL | 8.3499 mL | 16.6998 mL | |
| 5 mM | 0.3340 mL | 1.6700 mL | 3.3400 mL | |
| 10 mM | 0.1670 mL | 0.8350 mL | 1.6700 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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