U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of AN-9

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

HIDE SMILES / InChI

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

Description
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

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Esterase inhibitors diminish the modulation of gene expression by butyric acid derivative, pivaloyloxymethyl butyrate (AN-9).
1996 Dec
Molecular basis for the synergistic interaction of adriamycin with the formaldehyde-releasing prodrug pivaloyloxymethyl butyrate (AN-9).
2001 Nov 15
Formaldehyde-releasing prodrugs in combination with adriamycin can overcome cellular drug resistance.
2005
Epigenetics of cervical cancer. An overview and therapeutic perspectives.
2005 Oct 25
Activation of clinically used anthracyclines by the formaldehyde-releasing prodrug pivaloyloxymethyl butyrate.
2007 Apr
In vivo efficacy of a novel histone deacetylase inhibitor in combination with radiation for the treatment of gliomas.
2007 Apr
The anticancer prodrugs of butyric acid AN-7 and AN-9, possess antiangiogenic properties.
2007 Oct 18
The potential role of histone deacetylase inhibitors in the treatment of non-small-cell lung cancer.
2008 Oct
Phase I trial of vorinostat and doxorubicin in solid tumours: histone deacetylase 2 expression as a predictive marker.
2009 Oct 6
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
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
by admin
on Sat Dec 16 05:09:11 GMT 2023
Edited
by admin
on Sat Dec 16 05:09:11 GMT 2023
Record UNII
55VNK5440P
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AN-9
Common Name English
PIVANEX
Brand Name English
PIVALOYLOXYMETHYLBUTYRATE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C1934
Created by admin on Sat Dec 16 05:09:11 GMT 2023 , Edited by admin on Sat Dec 16 05:09:11 GMT 2023
Code System Code Type Description
DRUG BANK
DB05103
Created by admin on Sat Dec 16 05:09:11 GMT 2023 , Edited by admin on Sat Dec 16 05:09:11 GMT 2023
PRIMARY
CAS
122110-53-6
Created by admin on Sat Dec 16 05:09:11 GMT 2023 , Edited by admin on Sat Dec 16 05:09:11 GMT 2023
PRIMARY
FDA UNII
55VNK5440P
Created by admin on Sat Dec 16 05:09:11 GMT 2023 , Edited by admin on Sat Dec 16 05:09:11 GMT 2023
PRIMARY
PUBCHEM
60748
Created by admin on Sat Dec 16 05:09:11 GMT 2023 , Edited by admin on Sat Dec 16 05:09:11 GMT 2023
PRIMARY
NCI_THESAURUS
C1344
Created by admin on Sat Dec 16 05:09:11 GMT 2023 , Edited by admin on Sat Dec 16 05:09:11 GMT 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY