tcsc1324 Palifosfamide

Palifosfamide is a novel DNA alkylator and the active metabolite of ifosfamide, with antitumor activity.

In Vitro: Palifosfamide lysine (ZIO-201) is a stable form of palifosfamide. Palifosfamide lysine has broad activity in sarcoma lines in vitro. The IC₅₀ ranges from 2.25 ro 6.75 μM for most cell lines except OS222 (IC₅₀=31.5 μM)^[1].

In Vivo: Tumor growth inhibition is seen in both OS31 and OS33 xenografts and the RMS xenograft resulting in a significant difference in event-free survival between the control and the treated groups. Differential gene expression of ALDH3A1 but not ALDH1A1 is noted in the OS31 xenograft^[1]. Stabilized palifosfamide administered to mice suppresses MX-1 tumor growth by greater than 80% with 17% complete antitumor responses. Oral bioavailability in rats is 48-73% of parenteral administration, and antitumor activity in mice is equivalent by both routes. Treatment with palifosfamide-tris combined with docetaxelor doxorubicin at optimal regimens results in complete tumor regression in 62-75% of mice^[2].