application): HER2 is a transmembrane receptor tyrosine kinase overexpressed and amplified in nearly 30 percent of cancers. It is associated with poor prognosis, chemoresistance, and aggressive and metastatic tumor growth. Herceptin, a humanized monoclonal antibody to HER2, is currently available for treatment of metastatic breast cancer validating HER2 as an effective target for breast cancer treatment. However, problems associated with the use of antibodies as therapeutic agents are well known. Structural Bioinformatics Inc. used patented and proprietary drug design capabilities to extract 3D-pharmacophore structural information from computationally modeled dynamic protein HER2 kinase and used the pharmacophore information from this model to prescreen large-scale compound libraries for inhibitors of HER2 activity. Nine compounds showing IC50's < 20 uM in functional assays were obtained. The goal of Phase II is to perform computationally guided synthetic optimization and refinement of active lead compounds identified in Phase I and to discover selective and potent drug candidates active in various HER2 preclinical tumor models for advancement into clinical development. The long-term goal of the project is to develop a non-peptide potent and selective Herceptin-like drug for the treatment and prophylaxis of HER2 oncogene-mediated transformation, tumorigenesis, and metastasis

Proposed Commercial Applications

Not Available

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44CA082023-02
Application #
6211052
Study Section
Special Emphasis Panel (ZRG1-SSS-Z (01))
Program Officer
Lees, Robert G
Project Start
1999-04-01
Project End
2003-02-28
Budget Start
2001-03-01
Budget End
2002-02-28
Support Year
2
Fiscal Year
2001
Total Cost
$372,652
Indirect Cost
Name
Cengent Therapeutics, Inc.
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92127