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Pharmacyclics Reports Multiple Presentations at AACR on Its HDAC and Selective HDAC Inhibitors
Date:4/15/2008

overexpress the protein ErbB2, or

Her2, with PCI-24781 led to control of tumors in 80 percent of the

animals, with most achieving partial response.

-- Pharmacyclics researchers also presented a study identifying biomarkers

that may be useful in predicting the tumor sensitivity to treatment

with PCI-24781.

"These studies demonstrate that PCI-24781 may have a role in the treatment of cancers associated with overexpression of ErbB2 or HER2," said Joseph J. Buggy, Ph.D., vice president of research for Pharmacyclics. "We look forward to results from our ongoing Phase 1 study of this promising compound."

An additional study was presented on Pharmacyclics' PCI-34051, a novel, selective inhibitor of HDAC-8, a protein involved in T-cell leukemia that is also critical in immune function. In previous studies, PCI-34051 was shown to exhibit a greater than 200-fold selectivity to HDAC-8 compared with other HDAC enzymes. The compound selectively induced apoptosis, or cell death, in human T-cell lymphomas and leukemias in vitro. PCI-34051 exhibits anti-inflammatory properties, such as blocking secretion of cytokines from activated monocytes and other inflammatory cells, and has been shown to prevent hypersensitivity in animal models.

"We believe that PCI-34051 is a truly selective HDAC-8 inhibitor," said Sriram Balasubramanian, Ph.D., director of translational research for Pharmacyclics. "This study further demonstrates that blocking HDAC-8 has anti- inflammatory effects that may be useful for treatment of certain lymphomas and immune-mediated diseases."

About HDAC Inhibitors

Histone deacetylases are a family of related enzymes important in managing a multitude of cellular functions. HDAC inhibitors are a new class of drugs that modulate transcriptional activity in cells and may block angiogenesis and cell cycling, key components of tumor proliferation. HDAC inhibitors also appear to promote apoptosis (ce
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SOURCE Pharmacyclics, Inc.
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