TPI 287 A Third Generation Taxane

 

Dr. James McChesney

Tapestry Pharmaceuticals

CSO Natural Products Chemistry

 

 

Taxanes (paclitaxel and docetaxel) are highly active chemotherapeutic agents for the treatment of common advanced malignancies such as NSCLC and cancers of the breast, ovary, prostate and head and neck.  However, many of these neoplasms ultimately become resistant to the effects of currently available taxanes.  A taxane that could overcome resistance would be a valuable addition to the oncologic therapeutic armamentarium.  In the design of TPI 287, Tapestry Pharmaceuticals leveraged its extensive paclitaxel chemistry experience and understanding of taxane SAR in order to develop this novel taxane.  The specific attributes of MDR independence and retention of binding to modified tubulin were goals of the effort since these two mechanisms are thought to contribute to development of taxane resistance in solid tumors.The preparation, biological evaluation and preclinical development of TPI 287 will be described.