Small Molecule Centers
One of the most ambitious goals of the Roadmap has been the establishment of small molecule centers, which operate with cooperation between public organizations and private industry. These centers are the result of the New Pathways to Discovery theme and its Molecular Libraries initiative and are collectively called the NIH Molecular Libraries Screening Center Network.
In 2004, at the start of the practical application of the Roadmap initiatives, Discovery Partners International (DPI;www.discoverypartners.com) was looking at ways to move from being a producer of chemical libraries into a chemical library manager and saw involvement with the NIH Roadmap’s Molecular Libraries initiative as a way to demonstrate its abilities.
The NIH awarded DPI a $24-million, five-year contract to develop and maintain the NIH Molecular Libraries Small Molecule Repository (mlsmr.discoverypartners.com) and its associated website.
The repository was created to provide a public collection of organic chemicals for use in multiple NIH Screening Centers and to deposit the structures of these compounds into PubChem (pubchem.ncbi.nlm.nih.gov), the NCBI’s publicly accessible cheminformatics database of small organic molecules and their biological activity. The chemicals in the database are derived from public and private sources and include FDA-approved drugs, known compounds, compounds derived from natural templates, and new compounds generated by centers in the program.
One of the centers within the network is the New Mexico Molecular Libraries Screening Center (NMMLSC; screening.health.unm.edu). This center focuses on developing high-throughput flow cytometry assays, screening small molecules identified as targets by NIH partner institutions with this technology, and providing access to the screening data to both the public and private sectors.
According to Alexander Kiselyov, Ph.D., executive vp of R&D at ChemDiv (www.chemdiv.com), NMMLSC is the only public center capable of doing parallel FACS assays and committing to a pharma-like robust approach of reading up to 20 parameters at once.
As a result of previous collaboration with the University of New Mexico, Chemdiv was chosen to provide the chemicals used by the NMMLSC for screening biological targets.
Another center, the NIH Chemical Genomics Center (NCGC; www.ncgc.nih.gov) recently began collaborations with Invitrogen (www.invitrogen.com) and Genedata (www.genedata.com). Invitrogen provides cell-based assays for high-throughput screening at the center, and Genedata’s Screener software is used to compare and analyze high-throughput screening data across different assays.
"Our involvement with Roadmap stemmed from a conference Invitrogen held in April 2005 focused on the chemical genomics initiative," notes John Printen, R&D director of Invitrogen’s drug discovery solutions. "We saw a group of academians looking for the same screening that pharmaceutical companies have, and we looked into collaborating based on a new screening paradigm and how our cell-based tools could help the NCGC look at whole pathways of interaction"
According to Printen there was a high degree of interaction between Invitrogen and the screening center during this collaboration. "We provided access to cell-based assay sensors that were not yet on the market, giving NCGC the first look. They screened their chemicals with these assays, which demonstrated how useful these technologies are for various approaches. It has been a good intellectual exchange."
Invitrogen is also looking into the future for possible means of expanding its collaboration with the NCGC. "A lot depends on how this collaboration ends up," explains Printen. "We might apply some of our other technologies in the future, such as RNAi screening. We see a nice flow from the development of biological tools for screening of cell-based assays into labeling and visualization technology of molecular probes."