Aberrant epigenetic modifications are known to contribute to hematological and solid cancer malignancies. Members of an important class of chromatin modifying enzymes, histone deacetylases (HDACs), have been found to be dysregulated in many tumor types. Their specific contribution to oncogenesis is unknown, but numerous studies have linked increased HDAC inhibition to transcriptional repression of gene expression, cell cycle checkpoint activation and other tumor suppression activities. Therefore, HDAC inhibitors (HDACi) are an emerging and important class of modulators for use as single agents or in combination with other anti-neoplastics. Many current HDACi have undesirable off-target toxicities, which may be related to inhibition of specific HDAC isozymes that are required for normal cellular function. In an effort to rapidly and efficiently understand the beneficial and detrimental effects of new HDACi within a cellular context, we have developed a set of selective and pan-active bioluminogenic assay probes for evaluating the effects of HDACi. When multiplexed with same well fluorescent viability and cytotoxicity assays, these probes provide a functional readout of HDACi on-target efficacy and off-target safety in primary or cancer cell models.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B87.