A SMALL MOLECULE DRUG SPECIFIC FOR HER2 INHIBITION

DESCRIPTION (Adapted from the 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 APPLICATION: Not Available