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

Michal Entin-Meer, Ada Rephaeli, Xiaodong Yang, Abraham Nudelman, Ayelet Nudelman, Daphne Adele Haas-Kogan

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13 Scopus citations


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.

Original languageEnglish
Pages (from-to)205-214
Number of pages10
JournalCancer Letters
Issue number2
StatePublished - 18 Aug 2007

Bibliographical note

Funding Information:
This research was supported in part by the “Marcus Center for Pharmaceutical and Medicinal Chemistry” at Bar Ilan University, NIH-PO1 NS-42927-27A2 (D.A.H.-K., K.R.L.), NIH Brain Tumor SPORE Grant P50 CA097257 (D.A.H.-K., K.R.L.), The Nancy and Stephen Grand Philanthropic Fund, the Thrasher Research Fund, and the Israel Science Foundation Grant 542/00-4 (A.R. and A.N.).


  • AN-113
  • Glioma
  • HDAC inhibitor
  • Radiation potentiation
  • γ-H2AX


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