MEDI 334

Discovery, optimization and biological evaluation of novel, potent and selective histone deacetylase (HDAC) inhibitors

Nivedita D Namdev, nnamdev@arqule.com¹, Manish Tandon, mtandon@arqule.com¹, Rao Akireddy¹, Hernan Orgueira¹, David Vensel¹, Ming Kung¹, Hui Wu¹, Patrick Hutchins¹, Magdi Moussa¹, Jeffrey Link¹, Yanbin Liu¹, Robb Nicewonger¹, Charles Bruseo², Julie Gorenstein², Enkeleda Nakuci², Denise McSweeney², Karen Bresciano³, Yunxia Wang³, Dennis France², and Mark A. Ashwell⁴. (1) Medicinal Chemistry, ArQule Inc, 19 Presidential Way, Woburn, MA 01801, (2) Molecular Oncology, ArQule, Inc, 19 Presidential Way, Woburn, MA 01801, (3) Preclinical Development, ArQule Inc, 19 Presidential Way, Woburn, MA 01801, (4) ArQule Inc, 19 Presidential Way, Woburn, MA 01801

Histone deacetylase inhibitors (HDACi) have been pursued as a new class of targeted therapeutic agents for human cancer therapy. Here we describe the use of a high content screening assay measuring hyperacetylation together with HDAC enzyme inhibition data (IC50). Several series of potent HDAC in vitro inhibitors have been identified with differentiated HDAC isoform selectivity and anti-proliferative activity against cultured human cancer cell lines. The optimization of these series with parallel in vitro ADME assays is described.

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007