| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
HDAC; Bcr-Abl
Pivanex targets histone deacetylases (HDACs). HDACs are enzymes that remove acetyl groups from histone proteins, leading to chromatin condensation and transcriptional repression. Inhibition of HDACs results in histone hyperacetylation, which promotes a more open chromatin structure and activates the transcription of genes involved in cell cycle arrest, differentiation, and apoptosis. Pivanex also has antiangiogenic effects, reducing vascularization and expression of bFGF and HIF-1α. |
|---|---|
| ln Vitro |
Pivanex (100-500 μM) shows notable anti-proliferation activity in K562 cells[1].
Pivanex (100-500 μM) also increases caspase activity and apoptosis in K562 cells[1]. Pivanex (200 μM) causes a small reduction in G0-G1 and a moderate enhancement in the S and G2-M phases of the cell cycle[1]. Pivanex (AN-9) possesses specific toxicity to drug-resistant primary leukemia, acute leukemia, and cancer cell lines[2]. Pivanex demonstrates potent HDAC inhibitory activity in vitro. It inhibits HDAC enzymes, leading to histone hyperacetylation in cancer cells. This results in the upregulation of pro-apoptotic genes and downregulation of anti-apoptotic genes. The compound also shows antiangiogenic activity in vitro, inhibiting endothelial cell proliferation and tube formation. It downregulates Bcr-Abl protein and enhances apoptosis. Specific IC50 values for HDAC inhibition are not publicly available. |
| ln Vivo |
Pivanex (AN9, 200 mg/kg, b.i.d, daily) increases the SMN7 SMA mice's survival rate considerably. The end stage of the disease, which is indicated by the start of body mass loss, is also markedly delayed by pivanex (AN9) treatment[3].
Pivanex demonstrates in vivo anticancer activity in animal models. As an orally active compound, it is administered by oral gavage. It has antimetastatic and antiangiogenic properties. These effects are thought to occur by reducing vascularization and the expression of bFGF and HIF-1α. It has been investigated for cancer treatment. The compound's ability to induce apoptosis and inhibit tumor growth has been demonstrated in preclinical studies. |
| Enzyme Assay |
HDAC enzyme inhibition assays are performed using recombinant HDAC enzymes (HDAC1, HDAC2, HDAC3, HDAC6, etc.) or nuclear extracts from cancer cells. The enzyme is incubated with a fluorogenic substrate (e.g., acetylated lysine-AMC) in assay buffer. Deacetylation allows cleavage of the AMC group by trypsin, generating a fluorescent signal measured at excitation 360 nm, emission 460 nm. Test compounds are serially diluted and added to the reaction mixture. IC50 values are determined by non-linear regression analysis. Each concentration is tested in duplicate.
|
| Cell Assay |
Cell Line: K562 cells.
Concentration: 100-500 μM. Incubation Time: 24 hours. Result: Reduced the number of K562 viable cells significantly. 100 μM Pivanex with 0.125 or 0.25 μM STI571 reduced the number of viable cells synergistically. Cellular HDAC inhibition is evaluated in cancer cell lines (e.g., HeLa, MCF-7, A549). Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with Pivanex at various concentrations (0.1-100 μM) for 24-72 hours. Histone acetylation is measured by Western blotting using anti-acetyl-H3 and anti-acetyl-H4 antibodies. Cell viability is assessed using MTT or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V/PI staining, caspase-3/7 activity assays, and PARP cleavage. Angiogenesis is assessed by endothelial tube formation assays and VEGF secretion measurement. Each experiment includes known HDAC inhibitors (e.g., SAHA, TSA) as positive controls. |
| Animal Protocol |
SMN7 SMA mice (SMN2+/+; SMN7+/+; mSmn−/−).
200 mg/kg. Oral administration, b.i.d, at 09.00 and 17.00 daily. In vivo efficacy is evaluated in mouse xenograft models using human cancer cell lines. Pivanex is administered orally at doses typically ranging from 10-100 mg/kg/day. Tumor growth is monitored by caliper measurements. At study endpoint, tumors are harvested for histopathological analysis, immunohistochemistry (Ki67, CD31 for angiogenesis), and biochemical assays (HDAC activity, histone acetylation). Antimetastatic effects are evaluated in metastasis models. Body weight and clinical signs are monitored throughout the study. Sample sizes typically range from 6-10 animals per group. |
| ADME/Pharmacokinetics |
Pivanex has a molecular weight of 202.25 g/mol and a molecular formula of C10H18O4. Chemical name: [(2,2-dimethylpropanoyl)oxy]methyl butanoate. It is orally active. Solubility: soluble in DMSO. Storage: typically at -20°C. Bioavailability and half-life data are not publicly available. The compound is a research tool for studying HDAC inhibition and anticancer mechanisms.
|
| Toxicity/Toxicokinetics |
Limited toxicology data are available for Pivanex. As an HDAC inhibitor, potential toxicities may include effects on normal tissues, particularly rapidly dividing cells. Standard toxicology studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on hematopoiesis and gastrointestinal tract. No clinical trials have been reported for this compound. The compound is intended for research use only.
|
| References | |
| Additional Infomation |
The acyloxyalkyl ester prodrug of butyric acid (BA), neopentyloxymethylbutyrate (AN-9), exhibits low toxicity and significant anticancer activity both in vitro and in vivo. It is more effective than BA in inducing malignant cell differentiation and inhibiting tumor growth, and has shown superior toxicological, pharmacological, and pharmaceutical properties in preclinical studies. The acyloxyalkyl ester prodrug of butyric acid, neopentyloxymethylbutyrate, inhibits histone deacetylases, leading to cell differentiation, cell growth inhibition, and apoptosis. (NCI04)
Drug Indications It has been studied for the treatment of liver cancer, lung cancer, melanoma, and lymphoma. Mechanism of Action Neopentyloxymethylbutyrate is a histone deacetylase inhibitor and an analogue of butyric acid. It induces cell differentiation through signal transduction, thereby leading to apoptosis in cancer cells. Due to its high lipophilicity, it can rapidly and extensively enter cells and undergo esterase-mediated hydrolysis to generate neopentyl acid, formaldehyde, and butyric acid. Pivanex is also known as AN-9, AN9, pivaloyloxymethyl butyrate, and Titan. It is a novel and potent HDAC inhibitor with anticancer and antiangiogenic properties. It has antimetastatic properties. These anticancer activities are thought to occur by reducing vascularization and the expression of bFGF and HIF-1α. It has been investigated for cancer treatment. No clinical trials or regulatory approvals have been reported. The compound is for research use only. |
| Molecular Formula |
C10H18O4
|
|---|---|
| Molecular Weight |
202.2475
|
| Exact Mass |
202.121
|
| Elemental Analysis |
C, 59.39; H, 8.97; O, 31.64
|
| CAS # |
122110-53-6
|
| Related CAS # |
122110-53-6
|
| PubChem CID |
60748
|
| Appearance |
Colorless to light yellow liquid
|
| Density |
1.008g/cm3
|
| Boiling Point |
249.3ºC at 760mmHg
|
| Flash Point |
113ºC
|
| Vapour Pressure |
0.0231mmHg at 25°C
|
| Index of Refraction |
1.43
|
| LogP |
1.876
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
14
|
| Complexity |
203
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O(C([H])([H])OC(C([H])([H])C([H])([H])C([H])([H])[H])=O)C(C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])=O
|
| InChi Key |
GYKLFBYWXZYSOW-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C10H18O4/c1-5-6-8(11)13-7-14-9(12)10(2,3)4/h5-7H2,1-4H3
|
| Chemical Name |
butanoyloxymethyl 2,2-dimethylpropanoate
|
| Synonyms |
pivaloyloxymethyl butyrate; AN9; Pivanex; Titan
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: ≥ 100 mg/mL (~494.4 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (12.36 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (12.36 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (12.36 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.9444 mL | 24.7219 mL | 49.4438 mL | |
| 5 mM | 0.9889 mL | 4.9444 mL | 9.8888 mL | |
| 10 mM | 0.4944 mL | 2.4722 mL | 4.9444 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.
Link: https://clinicaltrials.gov/ct2/show/NCT00083473
Conditions:Leukemia, Lymphocytic, Chronic|Lymphoma, Small LymphocyticLink: https://clinicaltrials.gov/ct2/show/NCT00087477
Conditions:Malignant MelanomaLink: https://clinicaltrials.gov/ct2/show/NCT00073385
Conditions:Carcinoma, Non-Small-Cell LungProducts are for research use only; We do not sell to patients
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