| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
microtubule[1]
Taccalonolide AJ directly targets the microtubule/tubulin system. It binds covalently to the D226 residue of beta-tubulin. This covalent binding locks the exchangeable (E-site) of beta-tubulin into a GTP-preferred state, which promotes tubulin polymerization and prevents microtubule depolymerization. Its unique binding site and mechanism distinguish it from other microtubule stabilizers like taxanes. |
|---|---|
| ln Vitro |
Taccalonolide AJ exhibits potent antiproliferative activity against a range of cancer cell lines in vitro, including HeLa cells with an IC50 of 4.2 nM. It is effective against cell lines that overexpress multidrug resistance proteins. Mechanistically, it stimulates the polymerization of purified tubulin in a cell-free system and stabilizes preformed microtubules against cold- or CaCl2-induced depolymerization.
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| ln Vivo |
In vivo, Taccalonolide AJ has been evaluated in xenograft mouse models. While some forms like Taccalonolide AF and AJ have demonstrated potent in vivo antitumor efficacy, studies suggest that rapid microsomal clearance and a short half-life may limit the delivery of AJ to the tumor site, potentially reducing its observed antitumor activity in certain systems. However, it is generally considered a potent antitumor steroid.
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| Enzyme Assay |
A standard cell-free microtubule polymerization assay is used. Tubulin proteins are incubated with GTP in a reaction buffer at 37degC. The turbidity increase due to microtubule polymer formation is measured spectrophotometrically at 340 nm. Taccalonolide AJ is added to the reaction mixture to assess its ability to promote tubulin assembly. The compound can also be tested for competitive binding in a [3H]paclitaxel displacement assay to determine its binding site on tubulin.
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| Cell Assay |
For cellular assays, cancer cells (e.g., HeLa) are seeded in 96-well plates and incubated overnight. They are then treated with serial dilutions of Taccalonolide AJ (e.g., 0.1 nM to 10 uM) for 48-72 hours. Cell viability is assessed using a standard assay such as MTT or CellTiter-Glo. The half-maximal inhibitory concentration (IC50) is calculated from the resulting dose-response curves. Compound stock solutions are prepared in DMSO, and the final DMSO concentration is kept constant.
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| Animal Protocol |
For in vivo studies, immunocompromised mice (e.g., NOD-SCID) bearing subcutaneous tumor xenografts (e.g., HeLa or SCC-4) are used. Once tumors reach a suitable size, mice are treated intraperitoneally or subcutaneously with Taccalonolide AJ. A typical dosing schedule might be 0.5 mg/kg administered on days 1, 3, 5, and 8. Tumor volume is measured periodically with calipers, and endpoints include changes in tumor growth inhibition (TGI) and animal survival.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic (PK) properties for the AJ analog are limited. However, related taccalonolides are known to be rapidly metabolized. Studies indicate that the in vivo antitumor efficacy of some analogs can be limited by an increased rate of microsomal clearance and a decreased systemic half-life, which restricts drug delivery to the tumor. This suggests a potential challenge for achieving high and sustained plasma concentrations.
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| Toxicity/Toxicokinetics |
Detailed preclinical toxicity profiles for Taccalonolide AJ specifically are not well-documented in the available literature. As a microtubule-targeting agent, its toxicity profile may be associated with its mechanism of action, potentially causing side effects like peripheral neuropathy or myelosuppression, similar to other agents in its class. However, it is often noted for overcoming taxane resistance mechanisms.
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| References | |
| Additional Infomation |
The mechanism of action of Taccalonolide AJ is defined by its covalent binding to beta-tubulin D226, which locks the E-site of beta-tubulin into a GTP-preferred state, promoting polymerization. This unique mechanism allows it to circumvent taxane resistance mediated by tubulin mutations or multidrug resistance proteins. It has a distinct chemical structure compared to other microtubule stabilizers, and its discovery has provided new insights into the design of MSAs. No clinical trials or FDA approvals are reported; it is exclusively for research.
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| Molecular Formula |
C34H44O14
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|---|---|
| Molecular Weight |
676.70
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| Exact Mass |
676.273
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| CAS # |
2230777-09-8
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| PubChem CID |
56926890
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| Appearance |
White to off-white solid powder
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| Density |
1.48±0.1 g/cm3(Predicted)
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| Boiling Point |
779.0±60.0 °C(Predicted)
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| LogP |
0.6
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
48
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| Complexity |
1550
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| Defined Atom Stereocenter Count |
20
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| SMILES |
C[C@H]1[C@H]2[C@@H]([C@@H]([C@@H]3[C@@]2([C@H]([C@H]([C@H]4[C@H]3[C@H](C(=O)[C@@H]5[C@@]4([C@H]([C@@H]6[C@H](C5)O6)OC(=O)C)C)O)OC(=O)C)OC(=O)C)C)O)[C@]7([C@](C(=O)O[C@]78[C@H]1O8)(C)O)C
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| InChi Key |
BWKYBGRKQMTOQL-MPOFNYKTSA-N
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| InChi Code |
InChI=1S/C34H44O14/c1-10-17-20(32(7)33(8,42)29(41)48-34(32)26(10)47-34)23(40)18-16-19(25(43-11(2)35)28(31(17,18)6)45-13(4)37)30(5)14(21(38)22(16)39)9-15-24(46-15)27(30)44-12(3)36/h10,14-20,22-28,39-40,42H,9H2,1-8H3/t10-,14+,15-,16-,17-,18+,19+,20-,22+,23+,24-,25-,26-,27-,28-,30-,31+,32-,33+,34+/m0/s1
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| Chemical Name |
[(1S,2S,3R,5S,7S,9S,10R,11R,12S,13S,14R,15R,16S,17S,18S,20S,23S,24S,25R,26R)-10,14-diacetyloxy-3,23,26-trihydroxy-11,15,17,23,24-pentamethyl-4,22-dioxo-8,19,21-trioxaoctacyclo[13.11.0.02,12.05,11.07,9.016,25.018,20.020,24]hexacosan-13-yl] acetate
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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: 110 mg/mL (162.55 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 | 1.4778 mL | 7.3888 mL | 14.7776 mL | |
| 5 mM | 0.2956 mL | 1.4778 mL | 2.9555 mL | |
| 10 mM | 0.1478 mL | 0.7389 mL | 1.4778 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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