The study demonstrated that the uptake, efflux and cytotoxicity of Xanafide were unaffected by MDR proteins expressed in acute myeloid leukemia (AML) cells, and s-AML cells in particular, while other topoisomerase II inhibitors evaluated in this study were affected by the expression of these proteins.
The study investigated the transport and cytotoxicity of Xanafide and its active metabolite N-acetyl amonafide in leukemia and myeloma cell lines that over-express the MDR-associated proteins P-glycoprotein (Pgp), multi-drug resistance protein-1 (MRP-1) and breast cancer resistance protein (BCRP). Xanafide was also studied in pre-treatment marrow samples from s-AML patients that expressed these proteins. These results were compared to those of classical topoisomerase II inhibitors doxorubicin, daunorubicin, idarubicin, mitoxantrone and etoposide.
It was observed that the uptake, efflux and cytotoxicity of Xanafide did not differ in drug-resistant cell lines that over-expressed the MDR-related proteins when compared to non-resistant cell lines. The company believes Xanafide’s ability to maintain its AML cell uptake, as well as its cytotoxicity, in these cell types indicates that it may better reach therapeutic concentrations and maintain potency when compared to other drugs in its class.
Richard Dean, CEO of Xanthus, said: “Xanafide is currently in a Phase III trial under an SPA with the FDA, and we are hopeful that it will eventually become a much-needed option for patients facing this poor prognosis.”