CAMBRIDGE, Mass., Nov. 9 /PRNewswire/ -- NeoGenesis Pharmaceuticals, Inc., a privately held biopharmaceutical company focused on applying novel screening and chemistry technologies to discover and develop small molecule drugs, announced that they have demonstrated a new, powerful drug discovery technology for evaluating and optimizing the affinities of lead compounds for disease-associated protein targets.
In a study published today in the Journal of the American Chemical Society, NeoGenesis researchers document how their mass spectrometry-based Automated Ligand Identification System (ALIS) is used to simultaneously determine the affinities of individual compounds from a chemical mixture. When a purified protein is combined with a mixture of compounds, then titrated by a competitor compound, the affinities of each mixture component can be read directly from the resulting ALIS mass spectrometer responses. In addition, the competition profiles indicate whether the compounds are binding to the same site on the protein as the competitor, or whether they are binding to a different, allosteric site.
"Traditional methods of evaluating protein-ligand interactions, such as biochemical or functional assays, cannot discriminate which specific component of a compound mixture is contributing to the assay's result," explained Allen Annis, Ph.D., vice president of new technologies at NeoGenesis and the lead author of the study being published today. "The ALIS method solves this classic problem, and for the first time enables researchers to scrutinize the affinity and binding behavior of each component of the compound mixture. This method yields easy-to-interpret curves, which are very familiar to a pharmaceutical researcher, and the affinities can be simply read from left to right."
Henry Skinner, Ph.D., president and CEO of NeoGenesis Pharmaceuticals, Inc., said, "We are very excited about this breakthrough in drug discovery technology. A major roadblock that has prevented combinatorial chemistry from living up to its promise of faster, easier drug discovery has now been removed. Compound mixtures can be used directly and effectively to support medicinal chemistry optimization."
NeoGenesis' ALIS system for combinatorial chemistry has been used successfully for several years as a powerful, proven tool for discovering lead compounds from mixtures of hundreds to thousands of compounds. But this new, patent-pending approach has revolutionized the capabilities of the system by yielding affinity and mechanism of action measures that can support medicinal chemistry optimization.
NeoGenesis demonstrated this technique using targets of current interest in the pharmaceutical field, including the "resting state" (basal) form of the protein kinase Akt-1, an oncology target; and a G protein-coupled receptor (GPCR). "Determining the binding site to an inactive form of a receptor is a challenging task using traditional biochemical assays, although that information is vital for determining structure-activity relationships" said Huw Nash, Ph. D., vice president of chemical biology at NeoGenesis and a co- author of the study. "Compounds that bound to the basal kinase were shown by ALIS to select a site allosteric with respect to the active site of the protein."
"This new approach also has been successfully applied to a number of disease targets for collaborative and internal drug discovery programs in all classes of protein target space," added Nash.
About NeoGenesis Pharmaceuticals, Inc.
NeoGenesis Pharmaceuticals, Inc. is a drug discovery company which uses its proprietary affinity-based screening technologies and integrated chemical library and chemistry approaches to discover and develop a portfolio of small molecule drugs, both for itself and for its collaboration partners. The company's widely applicable and unbiased affinity-based technologies, coupled with its proprietary library of millions of diverse drug-like compounds, provide an unmatched efficiency in lead discovery and optimization. NeoGenesis' core technology, the Automated Ligand Identification System (ALIS), is a rapid, affinity-based system for identifying and optimizing novel drug leads that in many cases may not have been identified with traditional screening approaches. Coupled with the company's NeoMorph compound library, consisting of more than 5 million diverse medicinally-relevant small molecules, ALIS enables the identification and optimization of novel and selective drug leads against validated and emerging new targets. Founded in 1997 and headquartered in Cambridge, Massachusetts, NeoGenesis has developed partnerships and collaborative research agreements with many of the world's leading biotechnology and pharmaceutical companies, including: AstraZeneca, Amgen, Sanofi-Aventis, Biogen Idec, Celltech, Japan Tobacco, Merck, Mitsubishi Pharma, Pfizer, and Schering-Plough. Additional information about NeoGenesis may be found on the company's website at http://www.neogenesis.com/.
Note: NeoGenesis, ALIS and NeoMorph are trademarks of NeoGenesis Pharmaceuticals, Inc. All other trademarks are the property of their respective owners.
NeoGenesis Pharmaceuticals, Inc.