Aminoisoquinoline benzamides, FLT3 and Src-family kinase inhibitors, potently inhibit proliferation of acute myeloid leukemia cell lines.

Abstract

AIM Mutated or overexpressed FLT3 drives about 30% of reported acute myeloid leukemia (AML). Currently, FLT3 inhibitors have shown durable clinical responses but a complete remission of AML with FLT3 inhibitors remains elusive due to mutation-driven resistance mechanisms. The development of FLT3 inhibitors that also target other downstream oncogenic kinases may combat the resistance mechanism. RESULTS 4-substituted aminoisoquinoline benzamides potently inhibit Src-family kinases and FLT3, including secondary mutations, such as FLT3D835. Modifications of aminoisoquinoline benzamide to aminoquinoline or aminoquinazoline abrogated FLT3 and Src-family kinase binding. CONCLUSION The lead aminoisoquinolines potently inhibited FLT3-driven AML cell lines, MV4-11 and MOLM-14. These aminoisoquinoline benzamides represent new kinase scaffolds with high potential to be translated into anticancer agents.

DOI: 10.4155/fmc-2017-0067

Cite this paper

@article{Larocque2017AminoisoquinolineBF, title={Aminoisoquinoline benzamides, FLT3 and Src-family kinase inhibitors, potently inhibit proliferation of acute myeloid leukemia cell lines.}, author={Elizabeth Larocque and N Naganna and Xiaochu Ma and Clement Opoku-Temeng and Brandon A. Carter-Cooper and Gaurav Chopra and Rena G. Lapidus and Herman O. Sintim}, journal={Future medicinal chemistry}, year={2017}, volume={9 11}, pages={1213-1225} }