Advertisement
Histone deacetylases are a family of related enzymes important in managinga multitude of cellular functions. HDAC inhibitors are a new class of drugsthat modulate transcriptional activity in cells and may block angiogenesis andcell cycling, key components of tumor proliferation. HDAC inhibitors alsoappear to promote apoptosis (cell death) in tumor cells. Scientists have beensearching for more selective inhibitors, which may offer the potential fortreating a variety of diseases including cancer and inflammatory disorderswhile improving safety.
Advertisement
Results from the in-vitro study demonstrate that Pharmacyclics'proprietary HDAC inhibitor, PCI-34051, inhibits HDAC8 with 200-1000 foldselectivity over other HDAC enzymes. Studies showed that selective inhibitionof HDAC8 inhibits cell growth and induces apoptosis in cell lines derived fromT-cell lymphoma and leukemia, but not in other hematopoietic or solid tumorlines. This work also showed that HDAC8 selective inhibitors have a uniquemechanism of action, and could play a role in T-cell lymphoma and other immunemediated diseases.
"To our knowledge, this is the first description of a truly selective HDACisoform specific inhibitor," said Joseph J. Buggy, Ph.D., vice president ofresearch for Pharmacyclics. "This study also confirms that individual HDACisoforms have unique roles in cell physiology and it appears that the seriesof drug candidates we are developing may be useful in addressing diseasesmediated by T-cells such as T-cell lymphomas or certain immune-mediateddisorders."
The company's lead pan-HDAC inhibitor, PCI-24781, is currently in Phase 1clinical trials in patients with solid and hematologic tumors.
About Pharmacyclics
Pharmacyclics is a pharmaceutical company developing innovative productsto treat cancer and immune mediated diseases. The company is leveraging itssmall-molecule drug development expertise to build a pipeline in oncology andother diseases based on a wide range of targets, pathways and mechanisms. Moreinformation about the company, its technology, and products can be found athttp://www.pharmacyclics.com. Pharmacyclics(R), and the "pentadentate" logo(R)are registered trademarks of Pharmacyclics, Inc.
NOTE: Other than statements of historical fact, the statements made inthis press release about the initiation of and enrollment and future plans forour clinical trials, progress of and reports of results from preclinical andclinical studies, clinical development plans and product development andcorporate partnering activities are forward-looking statements, as defined inthe Private Securities Litigation Reform Act of 1995. The words "believe,""will," "may," "continue," "plan," "expect," "intend," "anticipate,"variations of such words, and similar expressions also identifyforward-looking statements, but their absence does not mean that the statementis not forward-looking. The forward-looking statements are not guarantees offuture performance and are subject to risks and uncertainties that may causeactual results to differ materially from those in the forward-lookingstatements. Factors that could affect actual results include risks associatedwith our ability to obtain future financing and fund the product developmentof our pipeline; the initiation, timing, design, enrollment and cost ofclinical trials and preclinical studies; the fact that data from preclinicalstudies and Phase 1 or Phase 2 clinical trials may not necessarily beindicative of future clinical trial results; our ability to establishsuccessf
