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For Immediate Release
Santa Fe, NM, August 10, 2004 - OpenEye Scientific Software, Inc. announces the release of WABE 1.3, a lead optimization program that generates analogs with the same shape but more desirable electrostatics. WABE is useful for exploring the chemical space around a lead compound to elucidate candidates with improved drug profiles or novel scaffolds to avoid patent coverage. "WABE has been shown to be capable of reproducing jumps between known patent classes for several important drugs," says OpenEye's Roger Sayle.
WABE quickly generates large numbers of isosteric analogs to a lead molecule, using a graph-invariant replacement algorithm. The method resembles the process of chemical substitution, e.g. carboxylate to amide or amidine, used in medicinal chemistry to create sets of molecules having the same physical shape but varying in electrostatics. WABE then scores the analogs by electrostatic similarity to a known binder or by protein-ligand binding. The similarities between analogs eliminate computationally demanding terms, so WABE efficiently scores over 10,000 analogs per second.
WABE learns the allowed atom-replacements from a user-specified training set of compounds, so it can avoid undesirable functional groups and generate chemistries suitable to a particular project. WABE can also constrain the atom-replacement to certain parts of the lead molecule, which is quite useful when elaborating structure activity relationship (SAR). Sayle points out, "WABE captures all the important SAR for a variety of systems, including methotrexate analogs binding to dihydrofolate reductase and for recently published inhibitors to Lck kinase."
About OpenEye
OpenEye Scientific Software was founded in 1997 to develop large-scale modeling applications and toolkits. Primarily geared towards drug discovery and design, areas of application include structure generation, docking, shape comparison, charge and electrostatics, chemical informatics and visualization. The software is designed for scientific rigor, as well as speed, scalability and platform independence. OpenEye makes most of its technology available as toolkits - programming libraries suitable for custom development. OpenEye software typically is distributable across multiple processors with PVM, supports 64-bit processing, and runs on Linux, Windows and Mac, as well as HP/Compaq, IBM, SGI and SUN flavors of UNIX.
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