Targeting Acute Myeloid Leukemia Using Sphingosine Kinase 1 Inhibitor-Loaded Liposomes

• DOI: 10.1021/acs.molpharmaceut.3c00078
• Publication Date: 2023-07-18T17:28:00Z
• Authors: Thao M. Nguyen; Manasi Jambhrunkar; Sook S. Wong; David M. Ross; Paul Joyce; John W. Finnie; Jim Manavis; Kristen Bremmell; Melissa R. Pitman; Clive A. Prestidge
• Keywords: Sphingosine Kinase

Acute myeloid leukemia (AML) kills 75% of patients and represents a major clinical challenge with need to improve on current treatment approaches. Targeting sphingosine kinase 1 novel ATP-competitive-inhibitor, MP-A08, induces cell death in AML. However, limitations MP-A08's "drug-like properties" (solubility, biodistribution, potency) hinder its pathway the clinic. This study demonstrates liposome-based delivery system MP-A08 that exhibits enhanced potency against AML cells. MP-A08-liposomes increased efficacy patient cells (>140-fold) significantly prolonged overall survival mice human disease (P = 0.03). The significant antileukemic property could be attributed specificity, bioaccessibility, bone marrow, as demonstrated pharmacokinetic biodistribution studies. Our findings indicate have potential for