New technique for affinity measurement in mixtures of chemical compounds
allows researchers to optimize drug leads with increased speed and greater
mechanistic insight
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.
SOURCE NeoGenesis Pharmaceuticals, Inc.
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Related links:
http://www.neogenesis.com
CONTACT:
Henry B. Skinner, Ph.D., President and CEO,
+1-617-588-5117, or Allen Annis, Ph.D., Vice President of New
Technologies, +1-617-588-5143, both of NeoGenesis
Pharmaceuticals, Inc.; or Bill Monigle, President of Bill Monigle
Associates, +1-603-424-1184
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