Subject: WABE 1.3 - electrostatics optimization of a lead compound

From: George Vacek <vacek$at$eyesopen.com>
Date: Thu, 23 Sep 2004 14:20:10 -0600

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 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."

For further information, please visit www.eyesopen.com or contact 
business$at$eyesopen.com.

Regards,
George Vacek
VP, Business Development
OpenEye Scientific Software