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Current | 2007 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001 | 2000 Celera Genomics And Syrrx Publish X-Ray Crystal Structure Of A Human Histone Deacetylase SOUTH SAN FRANCISCO, CA - July 14, 2004 Celera Genomics Group (NYSE:CRA), an Applera Corporation business, today announced publication in the journal Structure of the first three-dimensional x-ray crystal structure of a member of the class I histone deacetylases, human histone deacetylase 8 (HDAC8). HDAC enzymes can lead to the proliferation of cancer cells. Celera Genomics is investigating HDAC inhibitors in preclinical trials as potential treatments for cancer.
Researchers from Celera Genomics and Syrrx, Inc. determined the structure of human histone deacetylase 8 (HDAC8) bound to an experimental HDAC inhibitor synthesized by Celera Genomics, as well as the structures of other HDAC inhibitors currently under preclinical and clinical evaluation by other parties. The HDAC8 structure was determined using Syrrx's Nanovolume Crystallization® technology to crystallize disease-associated proteins. Celera Genomics and Syrrx are independently using the structure to design novel small-molecule HDAC inhibitors that may have advantages over current HDAC inhibitors undergoing evaluation.
“This structure provides new insights into how the HDAC’s function and a framework for identifying novel HDAC inhibitors,” said Robert Booth, Ph.D., Chief Scientific Officer of Celera Genomics. “Celera’s scientists have identified several novel inhibitors that exhibit in vivo efficacy in xenograft models of cancer, including one that reduced tumor volume by approximately 89% relative to untreated controls in a 17 day preclinical study.”
Histone deacetylation is carried out by a set of related HDAC enzymes and causes changes in DNA structures that can lead to the proliferation of cancer cells. Previously published studies indicate that inhibition of the HDAC enzymes can modulate cell growth rates, and in some cases, specifically induce the death of tumor cells. These data have fueled the design of small-molecule inhibitors of HDAC that are currently undergoing testing as potential treatments for major human diseases, including cancer.
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