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ActiveSight and CHDI Leverage Fragment-Based Lead Discovery for Huntington Disease Therapies
Date:9/18/2007

SAN DIEGO, Sept. 18 /PRNewswire/ -- ActiveSight, a division of Rigaku Americas Corporation, announced today that it will collaborate on a Fragment-based Lead Discovery (FBLD) Project with CHDI, Inc.

FBLD involves the binding of small compounds, "fragments," to the active sites of protein drug targets. The fragments are much smaller than the compounds used in traditional high-throughput screening (HTS), allowing a more extensive sampling of chemical space with a smaller screening library. Utilizing a Huntington Disease (HD) target chosen by CHDI, ActiveSight will screen fragment libraries using X-ray crystallography to visualize fragments that bind to the target. The fragments will then be linked or grown into larger, drug-like compounds that are thought to be more efficiently binding than compounds resulting from HTS methodologies.

Several compounds based on Fragment-based Lead Discovery (FBLD) methodologies are currently in clinical trials, and the technology is thought to shorten the time from drug target selection to an investigational new drug (IND) filing. The two companies hope that the FBLD collaboration will lead to HD therapies in shorter time periods than conventional lead discovery methods such as HTS.

"ActiveSight's Fragment-based Lead Discovery technologies strengthen our diversified portfolio of parallel drug discovery and development campaigns for Huntington Disease," said Robert Pacifici, Ph.D., CSO of CHDI, Inc. "By obtaining and testing high quality lead compounds quickly, we hope to increase the chances of finding a treatment for HD soon."

ActiveSight's high-throughput structural biology capabilities will facilitate rapid screening of CHDI's HD target with hundreds of drug-like fragments. Automated data collection and structural determination will be facilitated by Rigaku's tools for high-throughput X-ray crystallography, including the ACTOR(TM) crystal-mounting system robot and MIFit+ automated structural determination software. ActiveSight has leveraged these capabilities to screen several drug targets with their proprietary fragment libraries, and is pursuing lead development on promising fragment hits. The CHDI project will be overseen by Vicki Nienaber, Ph.D. at ActiveSight, a pioneer in the utilization of X-ray crystallography for Fragment-based screening and lead development.

"We are pleased to have the opportunity to work with CHDI to discover new treatments for Huntington Disease," said Duncan McRee, Ph.D., President of ActiveSight. "We will work closely with CHDI's drug discovery team to turn the results of our high-throughput FBLD screens into tightly binding lead compounds."

About Huntington Disease

Huntington Disease is a familial disease, passed from parent to child through a mutation in a gene. Each child of a Huntington Disease parent has a 50-50 chance of inheriting the Huntington Disease gene which causes programmed degeneration of brain cells and results in emotional disturbance, loss of intellectual faculties and uncontrolled movements. Most people with Huntington Disease develop the symptoms at midlife but in some people onset occurs in infancy or old age. The average survival time after onset is approximately fifteen to twenty years. It is estimated that about one in every 10,000 persons has the Huntington Disease gene. At this time, there is no way to stop or reverse the course of Huntington Disease.

About ActiveSight

ActiveSight(R) is a division of Rigaku Americas Corporation and is a leading provider of fragment-based lead discovery and structural biology for drug discovery. Utilizing high-throughput Rigaku X-ray crystallography instrumentation and world-class expertise, ActiveSight enables rapid lead discovery and development for its pharmaceutical, biotechnology, and institutional partners. For more information visit http://www.active-sight.com.

About CHDI, Inc. and High Q Foundation

CHDI, Inc. and the High Q Foundation, Inc. (High Q) are non-profit organizations that share the mission of bringing together academia, industry, governmental agencies, and other funding organizations in the search for Huntington Disease treatments.

CHDI, Inc. is pursuing a biotech approach to rapidly discover and develop drugs that prevent or slow Huntington Disease. Through collaborations with industrial and academic partners, CHDI, Inc. participates in all aspects of drug discovery and development from lead discovery to preclinical development. For more information about CHDI, Inc. and its collaborative programs please see http://www.chdi-inc.org.

High Q supports Huntington Disease research aimed at target identification and validation, the development and use of animal models, drug delivery, and the search for markers of disease progression. For more information about High Q and its support of Huntington Disease research please see http://www.highqfoundation.org.


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