| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
TLR9; Autophagy
(-)-Epipodophyllotoxin targets the mitotic spindle apparatus, a key structure involved in chromosome segregation during cell division. By inhibiting mitotic spindle assembly, the compound disrupts the normal progression of mitosis, leading to cell cycle arrest and ultimately cell death. The compound's antiproliferative activity against cancer cells is attributed to this mechanism. It also targets TLR9 and autophagy pathways, suggesting additional mechanisms of action. The compound serves as a structural scaffold for topoisomerase II inhibitors. |
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| ln Vitro |
Hydroxychloroquine Sulfate is a potent inhibitor of autophagy. It interferes with an essential step in the autophagic process by preventing lysosomal acidification. Treatment with HCQ reduces the growth of RCC (renal cell cancer) cells, boosts glycolysis, encourages apoptosis, and prevents mitochondrial oxygen consumption[2].
In vitro, (-)-Epipodophyllotoxin exhibits potent antiproliferative activity against cancer cells with GI50 values of 0.36 μM in HeLa cells and 0.24 μM in MCF-7 cells. It inhibits mitotic spindle assembly in vitro, which is the primary mechanism underlying its antiproliferative effects. The compound also targets TLR9 and autophagy pathways. These activities confirm (-)-Epipodophyllotoxin as a potent antimitotic agent with potential applications in cancer research. |
| ln Vivo |
In an in vivo rat model of I/R injury, hydroxychloroquine sulfate treatment reduces the infarct size, and the cardioprotective effect of hydroxychloroquine is ERK1/2 dependent[3].
Additionally, hydroxychloroquine sulfate exhibits an early protective effect on the vascular system. Endothelial dysfunction (ED) appears to be avoided in treated animals by HCQ[4]. Specific in vivo data for (-)-Epipodophyllotoxin are limited in the available literature. As a precursor to clinically used anticancer drugs (etoposide, teniposide), the compound's in vivo activity is primarily inferred from the pharmacology of its derivatives. Etoposide and teniposide are widely used in the clinic for the treatment of various cancers, demonstrating the therapeutic potential of the epipodophyllotoxin scaffold. However, (-)-Epipodophyllotoxin itself is primarily used as a research tool and starting material for drug synthesis rather than as a therapeutic agent. |
| Enzyme Assay |
Recombinant S6 protein and recombinant active P70S6K are used with purified proteins, and they are incubated in 1x kinase buffer with varying concentrations of HCQ or RAD001 in either the presence (25 μM) or absence of ATP for 30 minutes at 30°C. With the aid of phosphospecific antibodies and western analysis, total and phosphorylated S6 at the positions ser235/236 and ser240/244 are found. On the western blot, recombinant GST-tagged S6 (53 kd) can be distinguished from endogenous S6 (32 kd).
The antiproliferative activity is assessed using cell viability assays. Cancer cell lines such as HeLa (cervical cancer) and MCF-7 (breast cancer) are cultured in appropriate media and treated with (-)-Epipodophyllotoxin at various concentrations for 48-72 hours. Cell viability is measured using MTT, SRB (sulforhodamine B), or CellTiter-Glo assays. GI50 values (concentration causing 50% growth inhibition) are calculated from dose-response curves. Mitotic spindle assembly inhibition is assessed by immunofluorescence microscopy using anti-tubulin antibodies to visualize spindle morphology in treated cells. |
| Cell Assay |
All cells are cultured in RPMI containing 10% FBS, 1% glutamine, and 1% Pen/Strep. After overnight cell seeding on the appropriate plates, HCQ (75 or 100 μM) is applied for 48 hours.
For cellular studies, HeLa and MCF-7 cells are cultured in DMEM or RPMI-1640 supplemented with 10% FBS at 37°C in 5% CO₂. Cells are seeded in 96-well or 6-well plates and treated with (-)-Epipodophyllotoxin at various concentrations for 48-72 hours. Cell viability is assessed using standard colorimetric assays. For mitotic spindle analysis, cells are fixed and stained with anti-α-tubulin antibodies and DAPI for DNA, and analyzed by fluorescence microscopy. Cell cycle analysis is performed by flow cytometry after propidium iodide staining. |
| Animal Protocol |
In vivo studies for epipodophyllotoxin derivatives (etoposide, teniposide) are well established in mouse xenograft models and clinical trials. These compounds are administered intravenously or orally at various doses and schedules. However, specific in vivo protocols for (-)-Epipodophyllotoxin itself are not detailed in the available literature, as the compound is primarily used as a synthetic intermediate and research tool. For research purposes, standard xenograft protocols would apply if the compound were to be evaluated in vivo.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for (-)-Epipodophyllotoxin are not reported. The compound serves as the parent scaffold for etoposide and teniposide, which have well-characterized PK profiles. Etoposide has a half-life of 4-11 hours, moderate protein binding, and is eliminated primarily through renal and hepatic routes. However, (-)-Epipodophyllotoxin itself is not used therapeutically, and its PK properties would differ from its derivatives due to different physicochemical properties and metabolic pathways.
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| Toxicity/Toxicokinetics |
Toxicological data for (-)-Epipodophyllotoxin are limited. The compound is a potent antimitotic agent and should be handled with extreme caution. Its derivatives etoposide and teniposide are known to have significant toxicities including myelosuppression, gastrointestinal effects, and secondary malignancies. As a research compound, (-)-Epipodophyllotoxin should be handled in accordance with appropriate safety protocols for cytotoxic agents.
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| References | |
| Additional Infomation |
Reports have indicated that Juniperus sabina and Podophyllum peltatum contain podophyllotoxin, and relevant data exist. Podophyllotoxin is a lignan found in the resin of Podophyllum plants in their roots. It is a potent spindle toxin, toxic when ingested, and has been used as a laxative. Podophyllotoxin is highly irritating to the skin and mucous membranes, has keratolytic effects, and has been used to treat warts and keratosis. It may also possess antitumor properties, as do some of its homologues and derivatives.
(-)-Epipodophyllotoxin is a natural aryltetralin lignan from Podophyllum peltatum with potent antiproliferative activity (GI50: 0.36 μM in HeLa, 0.24 μM in MCF-7). It inhibits mitotic spindle assembly and serves as a precursor for etoposide and teniposide. No clinical trials or approvals exist for the parent compound. For research use only. |
| Molecular Formula |
C22H22O8
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|---|---|
| Molecular Weight |
414.40528
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| Exact Mass |
414.131
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| CAS # |
4375-07-9
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| Related CAS # |
4375-07-9
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| PubChem CID |
105111
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| Appearance |
Solid
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| Density |
1.37g/cm3
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| Boiling Point |
597.9ºC at 760 mmHg
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| Melting Point |
160.3 °C
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| Flash Point |
210.2ºC
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| Index of Refraction |
1.605
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| LogP |
2.409
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
629
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| Defined Atom Stereocenter Count |
4
|
| SMILES |
COC1C(OC)=CC([C@@H]2C3=CC4OCOC=4C=C3[C@@H](O)[C@H]3COC(=O)[C@H]23)=CC=1OC
|
| InChi Key |
YJGVMLPVUAXIQN-LGWHJFRWSA-N
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| InChi Code |
InChI=1S/C22H22O8/c1-25-16-4-10(5-17(26-2)21(16)27-3)18-11-6-14-15(30-9-29-14)7-12(11)20(23)13-8-28-22(24)19(13)18/h4-7,13,18-20,23H,8-9H2,1-3H3/t13-,18+,19-,20+/m0/s1
|
| Chemical Name |
(5S,5aR,8aR,9R)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
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| Synonyms |
(-)-Epipodophyllotoxin
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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) |
DMSO: ~87 mg/mL (~200.5 mM)
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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 | 2.4131 mL | 12.0653 mL | 24.1307 mL | |
| 5 mM | 0.4826 mL | 2.4131 mL | 4.8261 mL | |
| 10 mM | 0.2413 mL | 1.2065 mL | 2.4131 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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