Design and development of a next generation taxane

The Taxanes, Paclitaxel (Taxol) and Docetaxel (Taxotere) are among the most effective and clinically successful anti-cancer drugs ever developed. However, they show important clinical limitations in that they are subject to Multidrug Resistance (MDR) expression and some types of cancers are innately resistant to their action. Most patients relapse even after initial response, likely due to selection of multidrug resistance in the tumor cell population and regrowth of the tumor or MDR expressing metastases. Also the current clinically approved taxanes are unable to penetrate the CNS, an important site of metastases. TPI 287 has been designed to address the recognized limitations of current clinically approved taxanes. It is the first example of an abeo-taxane to show significant biological activity and has activity against MDR expressing tumors in preclinical animal models, is orally bioavailable and penetrates the CNS in vivo. TPI 287 is now in Phase II Clinical Development.

Structure of TPI-287