ActiveSight, a division of Rigaku Americas Corporation, 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, 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™ 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."