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Updated: Dec 23, 2025
Comet Assay to Quantify DNA Damage in FLT3 Mutant-expressing 32D Cells after Exposure to Type I and Type II FLT3 Inhibitors
Published on: October 17, 2025
Recent advances in FLT3 inhibitors for acute myeloid leukemia
Lexian Tong1, Xuemei Li1, Yongzhou Hu1
1ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
Abstract:
Fms-like tyrosine kinase-3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) cases, suggesting FLT3 as an attractive target for AML treatment. Early FLT3 inhibitors enhance antileukemia efficacy by inhibiting multiple targets, and thus had stronger off-target activity, increasing their toxicity. Recently, a number of potent and selective FLT3 inhibitors have been developed, many of which are effective against multiple mutations. This review outlines the evolution of AML-targeting FLT3 inhibitors by focusing on their chemotypes, selectivity and activity over FLT3 wild-type and FLT3 mutations as well as new techniques related to FLT3. Compounds that currently enter the late clinical stage or have entered the market are also briefly reported.
Insights
New FLT3 inhibitors show promise for treating acute myeloid leukemia (AML). These potent and selective drugs target FMS-like tyrosine kinase-3 (FLT3) mutations, offering improved efficacy and reduced toxicity compared to earlier treatments.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- FMS-like tyrosine kinase-3 (FLT3) mutations are present in about 30% of acute myeloid leukemia (AML) cases.
- FLT3 is a key therapeutic target for AML treatment.
- Early FLT3 inhibitors exhibited significant off-target activity and toxicity due to multi-targeting.
Purpose of the Study:
- To review the evolution of FLT3 inhibitors for AML treatment.
- To analyze the chemotypes, selectivity, and activity of FLT3 inhibitors against wild-type and mutated FLT3.
- To discuss emerging techniques related to FLT3 in AML therapy.
Main Methods:
- Literature review focusing on FLT3 inhibitor development.
- Analysis of inhibitor selectivity and activity profiles.
- Summary of compounds in late-stage clinical trials or on the market.
Main Results:
- Development of potent and selective FLT3 inhibitors effective against multiple FLT3 mutations.
- Demonstration of improved efficacy and reduced toxicity with newer generation inhibitors.
- Identification of promising FLT3-targeting agents progressing in clinical development.
Conclusions:
- Selective FLT3 inhibitors represent a significant advancement in AML therapy.
- These agents offer a more targeted approach with potentially better safety profiles.
- Ongoing research and development continue to refine FLT3-targeted strategies for AML.
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