Biochem/Physiol
Actions | MLN518 is a novel quinazoline-based small molecule inhibitor of the FLT3, KIT, and platelet-derived growth-factor receptor (PDGFR) tyrosine kinases with that has been shown to have great efficacy in murine models of FLT3 ITD-positive leukemia. Experiments with mice demonstrate that at effective concentrations, MLN518 has mild toxicity toward normal hematopoiesis for FLT3 ITD-positive leukemia. MLN518 has also been shown to preferentially inhibit the growth of blast colonies from FLT3 ITD-positive as compared to ITD-negative patients with AML, without significantly affecting colony formation by normal human progenitor cells. Tandutinib (MLN518, CT53518) is a potent FLT3 antagonist with IC50 of 0.22 μM, also inhibits PDGFR and c-Kit,15 to 20-fold higher potency for FLT3 versus CSF-1R and >100-fold selectivity for the same target versus FGFR, EGFR and KDR. |