0000000000615964
AUTHOR
Fian K. Mirea
showing 2 related works from this author
Bis(1H-indol-2-yl)methanones are effective inhibitors of FLT3-ITD tyrosine kinase and partially overcome resistance to PKC412A in vitro.
2009
Inhibition of the mutated fms-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase is a promising therapeutic strategy in acute myeloid leukaemia (AML). However, development of resistance to FLT3 tyrosine kinase inhibitors (TKI), such as PKC412A, has been described recently. This observation may have an increasing impact on the duration of response and relapse rates in upcoming clinical trials employing FLT3-TKI. Herein we investigated two representatives of a novel class of FLT3-TKI: Bis(1H-indol-2-yl)methanones. Both compounds effectively induced apoptosis in FLT3-internal tandem duplicate (ITD)-transfected murine myeloid cells and in primary FLT3-ITD positive blasts. Combination of bot…
3,4-Diarylmaleimides Effectively Inhibit Proliferation of FLT3-ITD-Positive Leukemic Cells, Induce Apoptosis and Show Additive Effects in Combination…
2007
Abstract Internal tandem duplication (ITD) mutations of FLT3 are present in leukemic blasts of approximately 30% of AML patients. ITD-mutations of FLT3 confer a worse prognosis and decreased overall survival. Therefore, FLT3-tyrosine kinase is considered an attractive drug target in AML and several FLT3-tyrosine kinase inhibitors (TKIs) are currently being tested in clinical trials (CEP701, MLN518, Sorafenib, PKC412). However, using these drugs as monotherapy, against the setting of remarkable efficacy has emerged the problem of short duration of remission indicating rapid development of secondary resistance. In addition, up to 30% of patients may show primary resistance to currently availa…