fosciclopirox + cytarabine

Fosciclopirox + cytarabine is an investigational combination therapy being studied for the treatment of relapsed or refractory acute myeloid leukemia (AML). Fosciclopirox (CPX-POM) is a prodrug that, after intravenous administration, is rapidly converted to its active metabolite ciclopirox. Ciclopirox acts as a γ-secretase inhibitor by binding to γ-secretase complex proteins Presenilin 1 and Nicastrin, which are essential for Notch activation. This results in inhibition of Notch 1 and Notch 2 expression and downstream signaling, leading to reduced proliferation and increased apoptosis in AML cells[1][2]. Cytarabine (ara-C) is an antimetabolite chemotherapeutic agent that inhibits DNA polymerase after being converted intracellularly into its active triphosphate form. It incorporates into DNA during the S phase of the cell cycle, causing direct DNA damage and blocking cell division[4][6][8]. The combination is currently under investigation in clinical trials for patients with relapsed/refractory AML who have failed prior therapies[1][3][5].