Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C10H18O4 |
| Molecular Weight | 202.2475 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCC(=O)OCOC(=O)C(C)(C)C
InChI
InChIKey=GYKLFBYWXZYSOW-UHFFFAOYSA-N
InChI=1S/C10H18O4/c1-5-6-8(11)13-7-14-9(12)10(2,3)4/h5-7H2,1-4H3
| Molecular Formula | C10H18O4 |
| Molecular Weight | 202.2475 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/18506586Curator's Comment: The description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/record/NCT00083473 | https://clinicaltrials.gov/ct2/show/NCT00087477 | https://clinicaltrials.gov/ct2/show/record/NCT00087477 | https://www.ncbi.nlm.nih.gov/pubmed/15715472
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18506586
Curator's Comment: The description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/record/NCT00083473 | https://clinicaltrials.gov/ct2/show/NCT00087477 | https://clinicaltrials.gov/ct2/show/record/NCT00087477 | https://www.ncbi.nlm.nih.gov/pubmed/15715472
Pivanex, also known as AN-9, is a histone deacetylase inhibitor analog of butyric acid that causes apoptosis of cancer cells through signaling cellular differentiation. AN-9 exhibited antimetastatic and antiangiogenic activities by reducing vascularization, bFGF expression, and HIF-1a. An important property of the AN-9 as anticancer agents is its ability to inhibit the growth of multidrug-resistant cancer cells including MCF- 7 Dx, HL-60Mx, and MES-SA-DX and to interact in synergy with doxorubicin in killing cancer cells. Combination of AN-9 and radiation significantly increased mortality of glioma cell lines and, in vivo, inhibited tumor growth and prolonged time to failure in mice bearing glioma xenografts, demonstrating their radiosensitizing function. In clinical trials. Pivanex is well tolerated in patients with advanced NSCLC and is indicative of anti-cancer activity.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2093865 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17267032 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Phase I trial of vorinostat and doxorubicin in solid tumours: histone deacetylase 2 expression as a predictive marker. | 2009-10-06 |
|
| The potential role of histone deacetylase inhibitors in the treatment of non-small-cell lung cancer. | 2008-10 |
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| Histone deacetylase inhibitors: the anticancer, antimetastatic and antiangiogenic activities of AN-7 are superior to those of the clinically tested AN-9 (Pivanex). | 2008 |
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| The anticancer prodrugs of butyric acid AN-7 and AN-9, possess antiangiogenic properties. | 2007-10-18 |
|
| Pivanex, a histone deacetylase inhibitor, induces changes in BCR-ABL expression and when combined with STI571, acts synergistically in a chronic myelocytic leukemia cell line. | 2007-08 |
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| Activation of clinically used anthracyclines by the formaldehyde-releasing prodrug pivaloyloxymethyl butyrate. | 2007-04 |
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| In vivo efficacy of a novel histone deacetylase inhibitor in combination with radiation for the treatment of gliomas. | 2007-04 |
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| Epigenetics of cervical cancer. An overview and therapeutic perspectives. | 2005-10-25 |
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| Formaldehyde-releasing prodrugs in combination with adriamycin can overcome cellular drug resistance. | 2005 |
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| Phase II trial of the histone deacetylase inhibitor pivaloyloxymethyl butyrate (Pivanex, AN-9) in advanced non-small cell lung cancer. | 2004-09 |
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| AN-9 (Titan). | 2004-06 |
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| Formation of mitoxantrone adducts in human tumor cells: potentiation by AN-9 and DNA methylation. | 2004 |
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| Mitoxantrone mediates demethylation and reexpression of cyclin d2, estrogen receptor and 14.3.3sigma in breast cancer cells. | 2003-07-25 |
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| Sequence specificity of adriamycin-DNA adducts in human tumor cells. | 2003-07 |
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| The histone deacetylase inhibitor AN-9 has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines. | 2002-11-01 |
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| A phase I study of pivaloyloxymethyl butyrate, a prodrug of the differentiating agent butyric acid, in patients with advanced solid malignancies. | 2002-07 |
|
| Molecular basis for the synergistic interaction of adriamycin with the formaldehyde-releasing prodrug pivaloyloxymethyl butyrate (AN-9). | 2001-11-15 |
|
| Doxorubicin and a butyric acid derivative effectively reduce levels of BCL-2 protein in the cells of chronic lymphocytic leukemia patient. | 2001-04 |
|
| Esterase inhibitors diminish the modulation of gene expression by butyric acid derivative, pivaloyloxymethyl butyrate (AN-9). | 1996-12 |
Patents
Sample Use Guides
2.5 g/m2 of Pivanex administered intravenously over 6 hours daily on Days 1 – 3. Treatment will be repeated every 21 days
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15715472
Uterine sarcoma (MES-SA, MES-DX5), Human prostate carcinoma (PC-3), colon cancer (HT-29) and myelocytic leukemia (HL-60, HL-60 MX2) cell lines were used for activity evaluation. Cells in 200-250 µL growth medium at a density of (2.5-5) × 10^4 cells/mL were seeded in tissue culture 96-well plates (in triplicate), for 24 h, without FCS. They were then exposed to different concentrations (titration) of the AN-9 (in medium containing 10% serum) under sterile incubation conditions. Two methods were used for proliferation measurements: (a) The Hoechst assay was used to examine the proliferation of the solid tumor cell lines HT-29, PC3, MES-SA, and MES-SA DX5. After 4 days of incubation with the AN-9, the samples were rinsed with PBS and fixed by the addition of 100 µL of 70% ethanol. After 0.5 h, the ethanol was decanted and 200 µL (10 mg/mL) of the DNA binding dye Hoechst reagent, solubilized in PBS, was added. The fluorescence emitted by the samples was measured at 390-460 nm; (b) The Alamar blue reagent (20 µL), used for HL-60, HL-60/MX2, , incubated at 37 °C, was added 24 h prior to termination of treatment, and the fluorescence was measured at 390 nm excitation and 460 nm emission (FluoStar fluorometer).
| Substance Class |
Chemical
Created
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Edited
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| Record UNII |
55VNK5440P
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| Record Status |
Validated (UNII)
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C1934
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DB05103
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122110-53-6
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55VNK5440P
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60748
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C1344
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