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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

Description

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.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown

PubMed

Sample Use Guides

In Vivo Use Guide
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
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).