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Updated: Jul 23, 2025

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

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

Thao M Nguyen^1,2, Manasi Jambhrunkar¹, Sook S Wong¹

¹Centre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia5001, Australia.

Molecular Pharmaceutics

|July 18, 2023

Summary

A novel liposome delivery system enhances MP-A08

Keywords:

acute myeloid leukemia liposomal drug encapsulation nanomedicine sphingosine kinase 1

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Area of Science:

Oncology
Pharmacology
Nanotechnology

Background:

Acute myeloid leukemia (AML) presents a significant clinical challenge with a high mortality rate.
Current treatments for AML require improvement.
MP-A08, an ATP-competitive inhibitor of sphingosine kinase 1, shows promise for AML treatment but has poor drug-like properties.

Purpose of the Study:

To develop a liposome-based delivery system for MP-A08 to overcome its limitations.
To evaluate the efficacy of MP-A08-liposomes against AML cells and in a preclinical model.

Main Methods:

Liposome formulation of MP-A08.
In vitro testing against patient-derived AML cells.
In vivo studies using a mouse model of human AML, including pharmacokinetic and biodistribution analysis.

Main Results:

MP-A08-liposomes demonstrated significantly enhanced potency against AML cells (over 140-fold increase).
Treatment with MP-A08-liposomes significantly prolonged overall survival in mice with human AML (P = 0.03).
Pharmacokinetic and biodistribution studies indicated enhanced specificity, bioaccessibility, and bone marrow delivery of MP-A08-liposomes.

Conclusions:

Liposome encapsulation improves the drug-like properties and therapeutic efficacy of MP-A08.
MP-A08-liposomes show potential as a novel and effective treatment strategy for acute myeloid leukemia.
This approach warrants further clinical investigation for AML patients.