| Size | Price | |
|---|---|---|
| 1mg | ||
| Other Sizes |
| Targets |
Farnesyltransferase (FTase / PFTase). Andrastin A is a meroterpenoid inhibitor that blocks the addition of a farnesyl isoprenoid group to the cysteine residue of the C-terminal CAAX motif of target proteins, most notably the Ras oncoprotein.
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|---|---|
| ln Vitro |
In cell-free enzyme assays, Andrastin A potently inhibits the enzymatic activity of farnesyltransferase, preventing the farnesylation of its protein substrates. It increases the accumulation and potentiates the effect of the chemotherapeutic agent vincristine in vitro, most likely by binding to plasma membrane phosphoglycoprotein to prevent the efflux of anticancer compounds from multidrug-resistant cancer cells.
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| ln Vivo |
In vivo antitumor activity has been demonstrated in preclinical models where it inhibits the farnesyltransferase activity of oncogenic Ras proteins. It has been shown to be effective in reducing tumor growth and, importantly, it inhibits the efflux of anticancer drugs from multidrug-resistant cancer cells, suggesting it could overcome P-glycoprotein (P-gp) mediated chemoresistance in vivo.
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| Enzyme Assay |
Standard non-cellular farnesyltransferase assays are performed using a 96-well plate format. Recombinant human FTase is incubated with a biotinylated peptide substrate. Andrastin A is added at varying concentrations. The reaction is initiated by adding [3H]-farnesyl pyrophosphate (FPP). After incubation, the reaction is stopped, and the farnesylated product is captured on streptavidin-coated membranes or plates and quantified by scintillation counting.
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| Cell Assay |
For cell-based P-glycoprotein inhibition assays, multidrug-resistant cancer cells (e.g., KB-V1 cells) are treated with Andrastin A (1-10 uM) in combination with a fluorescent P-gp substrate. The accumulation of the fluorescent substrate is measured by flow cytometry. An increase in intracellular fluorescence indicates inhibition of the drug efflux pump, confirming the compound's ability to reverse multidrug resistance.
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| Animal Protocol |
In vivo xenograft studies to assess chemosensitization are conducted. Nude mice bearing multidrug-resistant tumor xenografts are administered Andrastin A (e.g., intraperitoneally) in combination with a standard chemotherapeutic agent like vincristine. Tumor volume is measured, and at the end of the study, tumors are excised to measure the accumulation of the chemotherapeutic drug within the tumor tissue via HPLC-MS.
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| ADME/Pharmacokinetics |
Andrastin A is a natural product with high lipophilicity (logP ~3.2). It has a molecular weight of 486.60 g/mol and a molecular formula of C28H38O7. It is typically dissolved in DMSO for in vitro studies. For in vivo studies, it can be formulated in a vehicle containing oils or liposomes due to its poor water solubility. The compound is stable in powder form at -20degC.
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| Toxicity/Toxicokinetics |
Andrastin A is a known mycotoxin produced by Penicillium roqueforti, so it should be handled with care in a laboratory setting. Precise acute and chronic toxicity data are not fully detailed in public literature, but standard safety precautions for handling natural product mycotoxins apply, including avoiding inhalation, ingestion, and skin contact. It is not for human consumption.
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| References | |
| Additional Infomation |
There have been reports of the presence of Andrastin A in Penicillium, and relevant data are available for reference.
Andrastin A is not an FDA-approved drug. It remains a high-value chemical probe for studying the role of protein farnesylation in cancer biology. Its ability to inhibit both FTase and P-glycoprotein makes it unique, though it is recognized as a mycotoxin contaminant in stored food products due to its fungal source. |
| Molecular Formula |
C28H38O7
|
|---|---|
| Molecular Weight |
486.60
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| Exact Mass |
486.262
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| CAS # |
174232-42-9
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| PubChem CID |
6712564
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.19g/cm3
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| Boiling Point |
560.3ºC at 760 mmHg
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| Flash Point |
236.1ºC
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| Vapour Pressure |
1.39E-12mmHg at 25°C
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| Index of Refraction |
1.54
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| LogP |
3.869
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
35
|
| Complexity |
1060
|
| Defined Atom Stereocenter Count |
7
|
| SMILES |
CC1C(=O)[C@@]2(C(=C[C@@H]3[C@@]([C@@]2(C1=O)C(=O)OC)(CC[C@H]4[C@]3(CC[C@@H](C4(C)C)OC(=O)C)C=O)C)C)C
|
| InChi Key |
GRBXNADBNJGZRK-GJEDHNSHSA-N
|
| InChi Code |
InChI=1S/C28H38O7/c1-15-13-19-25(6,28(23(33)34-8)22(32)16(2)21(31)26(15,28)7)11-9-18-24(4,5)20(35-17(3)30)10-12-27(18,19)14-29/h13-14,16,18-20H,9-12H2,1-8H3/t16?,18-,19-,20+,25+,26+,27+,28-/m1/s1
|
| Chemical Name |
methyl (3S,5R,8S,9R,10S,13R,14R)-3-acetyloxy-10-formyl-4,4,8,12,13,16-hexamethyl-15,17-dioxo-2,3,5,6,7,9-hexahydro-1H-cyclopenta[a]phenanthrene-14-carboxylate
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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 | 2.0551 mL | 10.2754 mL | 20.5508 mL | |
| 5 mM | 0.4110 mL | 2.0551 mL | 4.1102 mL | |
| 10 mM | 0.2055 mL | 1.0275 mL | 2.0551 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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