AN-113, a novel prodrug of 4-phenylbutyrate with increased anti-neoplastic activity in glioma cell lines.

Abstract

Butyroyloxymethyl-4-phenylbutyrate (AN-113) is a novel HDACI that releases potent anti-neoplastic derivatives upon intracellular hydrolysis. The precursor of AN-113, 4-phenylbutyrate has shown promising results in a Phase I study of gliomas, and we hypothesized that AN-113 offers significant advantages over the parent drug. AN-113 demonstrates selective in vitro cytotoxicity against malignant cells while sparing normal astrocytes, effective at doses over 20-fold lower than 4-phenylbutyrate. Combining AN-113 and radiation results in additive therapeutic effects. Enthusiasm is lent to this approach by the ability of AN-113 to efficiently kill glioma cells, its bioavailability and potency when administered orally, its capacity to cross the blood-brain barrier, and its effectiveness in combination with radiation.

• Authors: Michal Entin-Meer, Ada Rephaeli, Xiaodong Yang, Abraham Nudelman, Ayelet Nudelman, Daphne Adele Haas-Kogan
• Journal: Cancer letters (Cancer Lett) Vol. 253 Issue 2 Pg. 205-14 (Aug 18 2007) ISSN: 0304-3835 [Print] Ireland
• PMID: 17346876 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Histone Deacetylase Inhibitors
• Phenylbutyrates
• Prodrugs
• butyroyloxymethyl 4-phenylbutyrate
• 4-phenylbutyric acid

Topics

• Antineoplastic Agents (metabolism, pharmacology)
• Astrocytes (drug effects, radiation effects)
• Blood-Brain Barrier (metabolism)
• Brain Neoplasms (enzymology)
• Cell Line, Tumor
• Cell Proliferation (drug effects, radiation effects)
• Glioma (enzymology)
• Histone Deacetylase Inhibitors
• Humans
• Phenylbutyrates (metabolism, pharmacology)
• Prodrugs (metabolism, pharmacology)