AN-113, a novel prodrug of 4-phenylbutyrate with increased anti-neoplastic activity in glioma cell lines
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- 作者：Michal Entin-Meer ; Ada Rephaeli ; Xiaodong Yang ; Abraham Nudelman ; Ayelet Nudelman ; Daphne Adele Haas-Kogan
- 关键词：AN-113 ; HDAC inhibitor ; Glioma ; Radiation potentiation ; γ ; -H2AX
- 刊名：Cancer Letters
- 出版年：2007
- 出版时间：18 August 2007
- 年：2007
- 卷：253
- 期：2
- 页码：205-214
- 全文大小：757 K
文摘
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.