AN-9

Names

[ Name ]:
AN-9

[Synonym ]:
pivaloyloxymethyl butyrate
Pivanex(TM)
((2,2-Dimethylpropanoyl)oxy)methyl butanoate
Pivanex
Butanoic acid,(2,2-dimethyl-1-oxopropoxy)methyl ester
Pivaloyloxymethyl butyrate Pivanex

Biological Activity

[Description]:

Pivanex (AN-9), a derivative of Butyric acid, is an HDAC inhibitor with antimetastic and antiangiogenic properties. Pivanex down-regulates bcr-abl protein and enhances apoptosis[1].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Cell Cycle/DNA Damage >> HDAC

Signaling Pathways >> Epigenetics >> HDAC

[In Vitro]

Pivanex (100-500 μM) exhibits significant anti-proliferation activity in K562 cells[1]. Pivanex (100-500 μM) also enhances apoptosis and caspase activity in K562 cells[1]. Pivanex (200 μM) induces enhancement in the G2-M phase, a moderate enhancement in the S phase and a slight reduction in G0-G1 of the cell cycle[1]. Pivanex (AN-9) has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines[2]. Cell Viability Assay[1] 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. Apoptosis Analysis[1] Cell Line: K562 cells. Concentration: 100-500 μM. Incubation Time: 6-72 hours. Result: Increased the number of K562 apoptotic cells significantly. Increased the caspase activity in K562 cells significantly after only 4 h of incubation with 500 μM.

[In Vivo]

Pivanex (AN9, 200 mg/kg, b.i.d, daily) significantly improves the survival of SMN7 SMA mice. AN9 treatment also marked delays the end stage of disease as defined by the onset of body mass loss[3]. Animal Model: SMN7 SMA mice (SMN2+/+; SMN7+/+; mSmn−/−)[3]. Dosage: 200 mg/kg. Administration: Oral administration, b.i.d, at 09.00 and 17.00 daily. Result: Improved the mean lifespan of treated SMN7 SMA mice by 84.6%. Delayed the onset of body mass loss in SMN7 SMA mice by 94.9%.

[References]

[1]. Rabizadeh E, et al. 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. Leuk Res. 2007 Aug;31(8):1115-23. Epub 2007 Jan 30.

[2]. Batova A, et al. The histone deacetylase inhibitor AN-9 has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines. Blood. 2002 Nov 1;100(9):3319-24.

[3]. Edwards JD, et al. Effect of the Butyrate Prodrug Pivaloyloxymethyl Butyrate (AN9) on a Mouse Model for Spinal Muscular Atrophy. J Neuromuscul Dis. 2016 Nov 29;3(4):511-515.

Chemical & Physical Properties

[ Density]:
1.008g/cm3

[ Boiling Point ]:
249.3ºC at 760mmHg

[ Molecular Formula ]:
C₁₀H₁₈O₄

[ Molecular Weight ]:
202.24800

[ Flash Point ]:
113ºC

[ Exact Mass ]:
202.12100

[ PSA ]:
52.60000

[ LogP ]:
1.87650

[ Vapour Pressure ]:
0.0231mmHg at 25°C

[ Index of Refraction ]:
1.43

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: EK7825000

CHEMICAL NAME :: Butanoic acid, (2,2-dimethyl-1-oxopropoxy)methyl ester

CAS REGISTRY NUMBER :: 122110-53-6

LAST UPDATED :: 199706

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C10-H18-O4

MOLECULAR WEIGHT :: 202.28

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Parenteral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1360 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 35,687,1992

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Articles

A phase I study of pivaloyloxymethyl butyrate, a prodrug of the differentiating agent butyric acid, in patients with advanced solid malignancies.

Clin. Cancer Res. 8(7) , 2142-8, (2002)

Pivaloyloxymethyl butyrate (AN-9), an acyloxyalkyl ester prodrug of butyric acid (BA), has demonstrated greater potency than BA at inducing malignant cell differentiation and tumor growth inhibition a...

Anticancer derivative of butyric acid (Pivalyloxymethyl butyrate) specifically potentiates the cytotoxicity of doxorubicin and daunorubicin through the suppression of microsomal glycosidic activity.

Mol. Pharmacol. 58(1) , 27-36, (2000)

Pivalyloxymethyl butyrate (AN9) is an anticancer derivative of butyric acid. In this study, doxorubicin (DXR) and AN9 synergistically inhibited the growth of lymphoma and lung carcinoma cells, whereas...

Effect of the cytostatic butyric acid pro-drug, pivaloyloxymethyl butyrate, on the tumorigenicity of cancer cells.

J. Cancer Res. Clin. Oncol. 123(5) , 267-71, (1997)

Previously we have shown that pivaloyloxymethyl butyrate (AN-9), a pro-drug of butyric acid (BA), is a differentiation-inducing agent in a variety of cells. In this report, we demonstrate that AN-9 is...