| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Targets |
Acevaltrate targets multiple cellular proteins and pathways. It is a dual inhibitor of PCBP1 (poly(rC)-binding protein 1) and PCBP2, as well as GPX4 (glutathione peroxidase 4), which are key regulators of ferroptosis, a form of iron-dependent programmed cell death. By inhibiting these targets, acevaltrate induces ferroptosis in cancer cells. Additionally, acevaltrate inhibits Na+/K+-ATPase, a membrane-bound enzyme that maintains cellular ion homeostasis, with IC50 values of 22.8 microM in rat kidney and 42.3 microM in rat brain hemispheres. It also inhibits rat P-type ATPases, including H+/K+-ATPase, with 60.7+/-7.3% inhibition at 100 microM. These diverse targets contribute to its cytotoxic and anticancer activities.
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| ln Vitro |
Acvaltrate differently inhibits rat P-type ATPase activity in vitro. At 100 µM, 60.7±7.3% blockage of rat H+/K+-ATPase can be accomplished [1].
Acevaltrate exhibits potent in vitro cytotoxic activity against various cancer cell lines. It shows high cytotoxicity against GLC4, a human small-cell lung cancer cell line, and COLO 320, a human colorectal cancer cell line, with IC50 values ranging from 1-6 microM. The compound inhibits Na+/K+-ATPase activity in rat kidney and brain hemispheres with IC50s of 22.8 microM and 42.3 microM, respectively. It also inhibits rat H+/K+-ATPase activity by 60.7+/-7.3% at 100 microM. As a ferroptosis inducer, acevaltrate inhibits PCBP1/2 and GPX4, leading to lipid peroxidation and cell death. Its ability to target multiple pathways makes it a potent anticancer agent in vitro. |
| ln Vivo |
In vivo studies on acevaltrate are limited. However, its potent in vitro activity against cancer cell lines and its ability to induce ferroptosis suggest that it may have antitumor activity in vivo. As a ferroptosis inducer, acevaltrate may be effective against tumors that are resistant to conventional apoptosis-inducing therapies. Its inhibition of Na+/K+-ATPase could also affect various physiological processes in vivo. Further studies are needed to evaluate its pharmacokinetics, toxicity, and efficacy in animal models. The compound's natural origin and diverse biological activities make it a promising lead for drug development, but additional preclinical studies are required.
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| Enzyme Assay |
The in vitro enzyme inhibition activity of acevaltrate can be assessed using cell-free assays. For Na+/K+-ATPase inhibition, a typical protocol involves incubating the enzyme with acevaltrate at various concentrations in a reaction buffer containing ATP, NaCl, KCl, and MgCl2. The reaction is carried out at 37degC for a specified period, and the amount of inorganic phosphate released from ATP hydrolysis is measured using a colorimetric assay. The IC50 value is determined by plotting the percentage of enzyme activity remaining against the compound concentration. For GPX4 inhibition, the enzyme is incubated with acevaltrate and a suitable substrate, and the activity is measured using a coupled assay or a fluorescent probe.
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| Cell Assay |
For in vitro cellular experiments, cancer cell lines (e.g., GLC4, COLO 320) are cultured in appropriate media and treated with acevaltrate at various concentrations (typically 0.1-100 microM). Cell viability is measured after 24-72 hours of treatment using MTT, CCK-8, or other cell proliferation assays. For ferroptosis studies, cells are treated with acevaltrate, and markers of ferroptosis, such as lipid peroxidation (measured by C11-BODIPY 581/591 fluorescence), glutathione depletion, and GPX4 expression, are assessed. The role of ferroptosis in acevaltrate-induced cell death can be confirmed using ferroptosis inhibitors such as ferrostatin-1 or liproxstatin-1. The duration of treatment and concentration of the compound can be optimized depending on the cell type and experimental objectives.
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| Animal Protocol |
In vivo animal experiments with acevaltrate are not well-documented in the available literature. However, given its in vitro anticancer activity and natural product origin, it could be evaluated in xenograft mouse models. A typical study would involve subcutaneous implantation of cancer cells in immunodeficient mice, followed by intraperitoneal or oral administration of acevaltrate at various doses. Tumor growth would be monitored by caliper measurements, and the compound's effect on tumor growth and survival would be assessed. Pharmacokinetic and toxicity studies would also be required to determine the optimal dosing regimen and safety profile. Further preclinical studies are needed to fully characterize its in vivo activity.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for acevaltrate are not well-documented in the available literature. As a natural product, its absorption, distribution, metabolism, and excretion properties would need to be characterized in preclinical studies. Its lipophilic nature and relatively low molecular weight may allow for oral absorption, but this has not been confirmed. The compound's stability in biological fluids and its metabolic pathways are also unknown. Further studies are needed to determine its bioavailability, half-life, and tissue distribution. These properties would be essential for evaluating its potential as a therapeutic agent.
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| Toxicity/Toxicokinetics |
The toxicity profile of acevaltrate has not been extensively characterized. Its inhibition of Na+/K+-ATPase, which is a critical enzyme for cellular ion homeostasis, suggests that it may have significant toxicity at high doses. However, its IC50 values for Na+/K+-ATPase inhibition are in the micromolar range (22.8 microM and 42.3 microM), which are higher than its cytotoxic IC50 values against cancer cells (1-6 microM). This suggests a potential therapeutic window. Its ability to induce ferroptosis could also lead to toxicity in normal tissues, particularly those with high iron content. Further toxicological studies are needed to assess its safety profile.
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| References | |
| Additional Infomation |
Acevaltrate is a fatty acid ester. It has been reported to be found in valerian, hornwort, and other organisms with relevant data.
Acevaltrate is a bioactive iridoid compound isolated from Valeriana glechomifolia. It is a novel ferroptosis inducer and a dual inhibitor of PCBP1/2 and GPX4. It also inhibits Na+/K+-ATPase activity in rat kidney and brain hemispheres with IC50 values of 22.8 microM and 42.3 microM, respectively. Acevaltrate exhibits high cytotoxicity against GLC4 (human small-cell lung cancer) and COLO 320 (human colorectal cancer) cell lines with IC50 values of 1-6 microM. It also inhibits rat P-type ATPases, including H+/K+-ATPase. The compound is a natural product with potential anticancer activity through the induction of ferroptosis. It is available as a research compound and is not approved for clinical use. |
| Molecular Formula |
C24H32O10
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|---|---|
| Molecular Weight |
480.5049
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| Exact Mass |
480.199
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| CAS # |
25161-41-5
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| PubChem CID |
65717
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
538.7±50.0 °C at 760 mmHg
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| Flash Point |
229.0±30.2 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.531
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| LogP |
1.91
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
34
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| Complexity |
915
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CC(C)CC(=O)O[C@H]1[C@H]2C(=C[C@@H]([C@]23CO3)OC(=O)CC(C)(C)OC(=O)C)C(=CO1)COC(=O)C
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| InChi Key |
FWKBQAVMKVZEOT-STCFVSJZSA-N
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| InChi Code |
InChI=1S/C24H32O10/c1-13(2)7-19(27)33-22-21-17(16(11-30-22)10-29-14(3)25)8-18(24(21)12-31-24)32-20(28)9-23(5,6)34-15(4)26/h8,11,13,18,21-22H,7,9-10,12H2,1-6H3/t18-,21+,22-,24+/m0/s1
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| Chemical Name |
[(1S,6S,7R,7aS)-4-(acetyloxymethyl)-1-(3-methylbutanoyloxy)spiro[6,7a-dihydro-1H-cyclopenta[c]pyran-7,2'-oxirane]-6-yl] 3-acetyloxy-3-methylbutanoate
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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: 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 (~208.12 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.33 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0812 mL | 10.4058 mL | 20.8117 mL | |
| 5 mM | 0.4162 mL | 2.0812 mL | 4.1623 mL | |
| 10 mM | 0.2081 mL | 1.0406 mL | 2.0812 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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