Description
Tandutinib is a potent antagonist of platelet-
derived growth factor receptor β (PDGFRβ), FLT3, and c-
Kit (IC
50 = 200, 220, and 170 nM, respectively). It less potently inhibits macrophage colony-
stimulating factor 1 receptor (IC
50 = 3.4 μM) and does not significantly inhibit other tyrosine or serine/threonine kinases. Tandutinib blocks the growth of cells expressing an internal tandem duplication within the juxtamembrane domain of the FLT3 receptor, found in some acute myelogenous leukemia cells. It also impairs the growth of colon cancer cells through its actions on the c-
Kit receptor. Tandutinib reverses multidrug resistance
in vitro by impairing the efflux activity of the multidrug resistance protein 7.
Chemical Properties
White Solid
Uses
An oral, small-molecule inhibitor of FLT3 for the treatment of AML (acute myelogenous leukemia)
clinical trials in patients with AML and myelodysplastic syndrome, but displayed promising antileukemic activity (90% complete remissions) in a phase I/II trial in patients with newly diagnosed AML w
hen administered in combination with cytarabine and daunorubicin.
Uses
An oral, small-molecule inhibitor of FLT3 for the treatment of AML (acute myelogenous leukemia) and other cancer indications. The drug exhibited limited activity as a single agent in phase I and II clinical trials in patients with AML and myelody
Definition
ChEBI: An N-arylpiperazine that is piperazine in which the hydrogen attached to the nitrogen at position 1 is replaced by a 6-methoxy-7-[3-(piperidin-1-yl)propoxy]quinazolin-4-yl group, while the hydrogen attached to the nitrogen at position 4
s replaced by a (p-isopropoxyphenyl)aminocarbonyl group. Tandutinib is an inhibitor of tyrosine kinases FLT3, PDGFR and KIT.
References
[1] kelly lm1, yu jc, boulton cl, apatira m, li j, sullivan cm, williams i, amaral sm, curley dp, duclos n, neuberg d, scarborough rm, pandey a, hollenbach s, abe k, lokker na, gilliland dg, giese na. ct53518, a novel selective flt3 antagonist for the treatment of acute myelogenous leukemia (aml). cancer cell. 2002 jun;1(5):421-32.
