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.
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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)
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Chemical References |
- Antineoplastic Agents
- Histone Deacetylase Inhibitors
- Phenylbutyrates
- Prodrugs
- butyroyloxymethyl 4-phenylbutyrate
- 4-phenylbutyric acid
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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)
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