Investigator:  Lynnie Trzoss, University of Rhode Island

Mentor:  David Rowley, University of Rhode Island

Scientific Theme:  Cancer

Abstract:  Acute myeloid leukemia (AML) is the most common form of leukemia and the most common cause of leukemia death. Current anticancer treatments against acute Leukemia heavily rely on generally cytotoxic agents. One of the most common liabilities of generally cytotoxic agents is the severe side effects. This has encouraged the search for new drugs with selectivity for single cancer types could lead personalized cancer treatments with greatly reduced or eliminated side effects.

Penisimplicissin, a vermistatin-type of natural product, displayed potent and selective activity against acute leukemia cell lines CCRF-CEM and HL-60 in the NCI-60 cell line panel. However, due to the limit supply fromnatural source,the underlying mechanism has not been elucidated. We therefore propose to synthesize penisimplicissin and fluorescent-labeledpenisimplicissinto initiate advanced biological evluations.

Our long-term goal is to provide molecular and cellular details on how penisimplicissin induces antiproliferative effects against acute leukemia, and to develop novel vermistatin-type molecular inhibitors against acute leukemia. Our approach is different from previously described inhibitors against acute leukemia, such as FLT3 inhibitors AC220 and SU11248. These agents were designed as ATP binding site kinase inhibitors and are often less selective. Penisimplicissin is expected to offer a new class of inhibitor against leukemia with a novel mechanism of action.

Human Health Relevance:  Discovery of a novel theraupetic target against actue leukemia. Development of novel inhibitors against actue leukemia.