>>Monday August 27, 3:15 pm Eastern Time
Press Release
SOURCE: Corvas International, Inc.
Corvas Presents 3-D Molecular Structure of Matriptase, First Structural Insight Into New Class of Protease Cancer Targets
- Company Outlines Its Strategy for Exploiting the Serine Protease Gene Family for New Solid Tumor Cancer Therapies at ACS Meeting -
CHICAGO, Aug. 27 /PRNewswire/ -- Corvas International, Inc. (Nasdaq: CVAS - news) reported today that Company scientists and collaborators at the Max-Planck Institute of Biochemistry in Martinsried, Germany, have solved the three-dimensional molecular structure of the functional domain of matriptase, a newly identified serine protease target for breast and prostate cancer drug development. This new structural information is expected to facilitate the design of drugs that block or otherwise exploit the activity of matriptase and related proteases. Corvas also presented its strategy for the discovery and development of new solid tumor cancer therapies that target the serine protease gene family at the 222nd National Meeting of the American Chemical Society today in Chicago, IL.
``Matriptase is the first member of a distinct family of cancer-associated, transmembrane serine proteases to be characterized at the molecular level,'' said Edwin Madison, Ph.D., Vice President of Biological Research, who presented for Corvas. ``We intend to use matriptase as a target itself and as the model protease for this gene family to accelerate the rational design and optimization of drugs to treat solid tumor cancers. With our collaborators at Max-Planck, we have already generated several proprietary high resolution 3-D structures of matriptase bound to lead small molecule inhibitors.'' Inhibitors have therapeutic potential as drugs for the treatment or prevention of disease and are used as research tools to validate the role of proteases in disease.
Unlike most proteases, which are either secreted from or retained in the cell, transmembrane serine proteases are located on the cell surface. This confined location may offer a unique opportunity to target cancer treatments directly to diseased tumor cells thereby avoiding damage to healthy cells and tissues, a serious problem associated with many current therapies, including radiation and chemotherapy. In this regard, several recent reports in leading scientific journals have implicated hepsin, another transmembrane serine protease related to matriptase, as a biological marker of, and potential drug target for, prostate cancer.
Corvas is currently working to validate the role of matriptase and other serine protease targets in animal models of breast and prostate cancer. The Company employs a functional genomics approach to discover and validate targets, which includes initially cloning the full-length gene sequence and producing the functional domain of the protease. These initial steps provide the biological materials necessary for the development of high throughput methods to screen potential lead drug candidates, including small molecule protease inhibitors, which are then used in animal models for target validation.
``We believe that a combination of therapeutic approaches that attack cancer on multiple fronts will be essential to improve upon current standards of care,'' said George P. Vlasuk, Ph.D., Chief Scientific Officer at Corvas. ``Accordingly, our cancer strategy includes the development of synthetic small or organic molecules, monoclonal antibodies, small protein inhibitors and prodrug therapies, all of which may be advanced through structure-based drug design.''
Background: Corvas' serine protease cancer drug programs
The modulation of serine protease activity associated with solid tumors is the foundation of Corvas' discovery platform to develop new therapeutic strategies for the treatment of cancer. This effort includes the discovery and validation of novel serine protease targets that may play a role in angiogenesis or tumor growth and progression, as well as the validation of known proteases that have not been previously implicated in these processes. Target discovery coupled with Corvas' medicinal chemistry expertise in the design and synthesis of proprietary small molecule inhibitors of serine proteases provides a comprehensive discovery platform that the Company believes will accelerate the development of novel therapeutic approaches to solid tumor cancers.
Corvas' expertise in protease modulation has been developed in conjunction with the Company's cardiovascular (thrombosis or blood clotting) and infectious disease (hepatitis C virus infection) programs that are based on synthetic small molecule inhibitors of serine proteases. Corvas has an active medicinal chemistry based program in the design of inhibitors to urokinase plasminogen activator (u-PA). u-PA is a serine protease that has been implicated in the growth and progression of certain solid tumor cancers such as breast cancer. Highly selective and potent small molecule lead inhibitors of u-PA have been shown to inhibit angiogenesis and tumor growth in animal models. The Company has identified more than 70 cancer-associated proteases and has filed patents on several full-length gene sequences including high throughput screening methods for the respective proteases.<<
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