Synthetic apratoxins and novel analogs for anticancer and therapeutic applications
T2018-101 Synthetic natural apratoxins and non-natural apratoxin analogs with improved pharmacokinetic profiles for cancer treatments and drug development applications.
Apratoxins are potent cytotoxic biosynthetic products that are naturally produced by specific marine microorganisms. When isolated from organisms, the compounds display very potent anticancer activities. In addition, they have been implicated in immunosuppressive activity. However, in their natural form, apratoxins have a narrow therapeutic window, are poorly tolerated in animal studies, and are too toxic for direct use as chemotherapeutics. Additionally, due to a limitation on accessibility, isolation for use on a large scale is not feasible for commercial use. Thus, there remains a need for analogs of these natural apratoxins that have improved physiological properties, such as reduced toxicity, while still being useful for targeted treatment of tumors.
Researchers at The Ohio State University led by Dr. Craig Forsyth have developed laboratory syntheses of natural apratoxins and non-natural apratoxin analogs. Some of these analogs are designed to be used to elucidate cellular binding partners in efforts to determine their anticancer mechanisms, and others for the empirical identification of therapeutic candidates with enhanced selectivities for cancerous cells versus non-transformed cells. These synthetic variants could also be used to develop treatments for solid tumors, without a need to extract material from natural sources.
- Cancer treatment in combination with current therapeutics
- Drug development for solid tumors
- Potent anticancer agents with less toxicity compared with original apratoxin
- Useful to elucidate anti-cancer mechanisms of action for cancer treatment development