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Updated: Aug 5, 2026

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Development of Novel Schiff Base-Tyrosine Kinase Inhibitor Conjugates that Enhance the Effects of ALA-PDT
Yusei Shinohara1, Chiaki Abe2, Yoshio Endo3
1Graduate School of Technology, Industrial and Social Science, Tokushima University, Tokushima, Japan.
Background/Aim:
Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) is a widely accepted and minimally invasive treatment for various cancers. The Schiff base derivative N-3',5'-dichloro-2'-hydroxybenzylidene-2-chloro-4-nitroaniline (TX-816) markedly enhances the efficacy of ALA-based PDT (ALA-PDT) by promoting intracellular accumulation of protoporphyrin IX (PpIX). However, TX-816 is unstable in aqueous solutions and rapidly hydrolyzes into the active agent 3, 5-dichlorosalicylaldehyde (DCSA) and 2-chloro-4-nitroaniline, thereby complicating its clinical application.
Materials And Methods:
We synthesized UTX-144 (a dasatinib derivative) and UTX-148 (a gefitinib derivative) by conjugating the tyrosine-kinase inhibitors dasatinib or gefitinib with DCSA via a Schiff base. These novel ALA-PDT sensitizers conjugate tyrosine kinase inhibitors (TKIs) that target ATP-binding cassette subfamily G member 2 (ABCG2), a PpIX efflux transporter, with DCSA via a Schiff base.
Results:
UTX-144 and UTX-148 showed strong ALA-PDT sensitization effects when used in combination with ALA, thereby increasing intracellular PpIX accumulation.
Conclusion:
This study successfully developed the novel ALA-PDT sensitizers UTX-144 and UTX-148.
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