Ralph R. Barry
Vice President, Chief Financial Officer

Susan K. Burgess, Ph.D.
Vice President Corporate Development

Structural Bioinformatics Inc.
10929 Technology Place
San Diego, CA 92127
Tel: (619) 675-2400
Fax: (619) 451-3828
http://www.strubix.com
 

 SAN DIEGO, CA - (July 27, 1998) Structural Bioinformatics Inc. ("SBI"), San Diego has successfully combined its computational technologies covering dynamic protein surface generation and analysis, dynamic pharmacophore template generation (SBI's DynaPharm™ technology) and protein structure-guided virtual combinatorial library generation (SBI's CombiLib™ technology), to generate a number of small-molecule non-peptide TNF (tumor necrosis factor) receptor antagonist lead molecules suitable for refinement into drug candidates for various inflammatory diseases such as rheumatoid arthritis.

Using dynamic protein surface information derived from TNF, SBI scientists used proprietary methods to create a virtual construct of the predicted shape of small-molecule TNF antagonists. This virtual construct, called a DynaPharm™ template, was used to screen a selected module of SBI's CombiLib™ database containing 136,000 virtual molecules having a common drug-like organic chemical scaffold computationally. A total of 15 molecules were selected for synthesis and testing. All 15 molecules synthesized and tested demonstrate some level of TNF receptor antagonist activity. Four molecules are sufficiently active and specific so as to qualify as valid optimization candidates, and all 15 molecules are useful in SAR analysis. The novel structures are the subject of patent applications in preparation. The entire discovery process, including synthesis and testing, was conducted over a period of approximately 3 months beginning earlier this year. SBI will seek corporate partners to further develop and eventually market TNF antagonists derived from its proprietary lead discovery and optimization technology.

Dr. Edward T. Maggio, SBI's Chairman and President said: "SBI's use of its proprietary dynamic protein structure technologies to focus combinatorial synthesis will have a major impact upon the speed and cost of future drug discovery efforts. Our technology makes it possible, for the first time, to take maximum advantage of the two major dynamics reshaping the pharmaceutical industry today, namely the availability of molecular diversity on a truly grand scale through the advent of combinatorial chemistry, and the availability of thousands of new protein targets as a result of the human genome project and other gene sequencing efforts around the world."

Structural Bioinformatics has developed a supercomputational operating system making possible the immediate and practical use of genomic (gene sequence) data in a broad range of structure-based drug discovery and design processes leading to the rapid design and identification of small-molecule lead compounds. SBI is building corporate partnerships with pharmaceutical companies, gene discovery companies, and combinatorial chemistry companies ranging from broad technology collaborations to assistance with specific drug targets or target groups. Current corporate collaborators include Biochem Pharma, Ltd., Yamanouchi Pharmaceutical Co. Ltd., and a second undisclosed major Japanese Pharmaceutical company.