Title:Chemical Space of FLT3 Inhibitors as Potential Anti-AML Drugs
Volume: 12
Issue: 4
Author(s): Qing-Yuan Lan, Yan-Le Zhi, Hao Heng, Jie-Yi Tian, Xiao-Xing Guo, Hai-Chun Liu, Ya-Dong Chen, Tao Lu*Shuai Lu*
Affiliation:
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009,China
- Laboratory of Molecular Design and Drug Discovery, China Pharmaceutical University, Nanjing 211198,China
Keywords:
Acute myeloid leukemia, drug resistance, clinical advance, Fms-like tyrosine kinase 3, patent, receptor tyrosine
kinase inhibitor.
Abstract: Background: FLT3 is a member of receptor tyrosine kinase III family, mainly expressed in
hematopoietic cells. The aberrant expression and function of FLT3 are strongly related to leukemia,
especially acute myeloid leukemia. Its varieties of amino-acid residues mutations, such as FLT3-ITDs
and -TKDs, can induce constant proliferation of hematological tumor cells with poor prognosis. Hence
FLT3 serves as a promising target in AML chemotherapy.
Objective: This review focused on the progress of FLT3 inhibitors study including those that have entered
clinical trials or were reported in numerous patents all over the world. Thus, we provided a useful
reference for the development of new anti-leukemia drugs.
Method: Through a comprehensive retrospective study, FLT3 inhibitors in several patent applications
were identified and classified into five categories, including quinolone-related, indole-related, ureas,
pyrimidines and other compounds.
Results: For each category of compounds, the structural feature, SAR, biological activity and current
research status were thoroughly reviewed and analyzed.
Conclusion: Although some of those compounds expressed potent bioactivities and have reached the
advanced clinical trials for the treatment of leukemia, there are still several problems need to be faced
before they enter the market eventually, especially the drug resistance issue. The improvement of therapeutic
potency for FLT3 inhibitors might depend on the useful combination therapy and further refinement
of the intrinsic properties of FLT3 inhibitors.
