Targeting Acute Myeloid Leukemia Using Sphingosine Kinase 1 Inhibitor-Loaded Liposomes.
Date
2023
Authors
Nguyen, T.M.
Jambhrunkar, M.
Wong, S.S.
Ross, D.M.
Joyce, P.
Finnie, J.W.
Manavis, J.
Bremmell, K.
Pitman, M.R.
Prestidge, C.A.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Molecular Pharmaceutics, 2023; 20(8):3937-3946
Statement of Responsibility
Thao M. Nguyen, Manasi Jambhrunkar, Sook S. Wong, David M. Ross, Paul Joyce, John W. Finnie, Jim Manavis, Kristen Bremmell, Melissa R. Pitman, and Clive A. Prestidge
Conference Name
Abstract
Acute myeloid leukemia (AML) kills 75% of patients and represents a major clinical challenge with a need to improve on current treatment approaches. Targeting sphingosine kinase 1 with a novel ATP-competitive-inhibitor, MP-A08, induces cell death in AML. However, limitations in MP-A08’s “drug-like properties” (solubility, biodistribution, and potency) hinder its pathway to the clinic. This study demonstrates a liposome-based delivery system of MP-A08 that exhibits enhanced MP-A08 potency against AML cells. MP-A08-liposomes increased MP-A08 efficacy against patient AML cells (>140-fold) and significantly prolonged overall survival of mice with human AML disease (P = 0.03). The significant antileukemic property of MP-A08-liposomes could be attributed to its enhanced specificity, bioaccessibility, and delivery to the bone marrow, as demonstrated in the pharmacokinetic and biodistribution studies. Our findings indicate that MP-A08-liposomes have potential as a novel treatment for AML.
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Dissertation Note
Provenance
Description
Data source: Supporting information, https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.3c00078?goto=supporting-info
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© 2023 American Chemical Society