RK-20449 (A419259) is a potent, small molecule inhibitor of hematopoietic cell kinase (HCK) with IC50 of 0.43 nM.
RK-20449 displays an IC50 <100 nM against 7 kinases in a panel of 107 human kinases, all of which are SFKs (FYN, HCK, LCK, LYNa, LYNb, SRC, and YES), consistent with the high level of amino acid sequence homology among the SFKs.
RK-20449 potently inhibits CD34+ CD38− human primary AML cell proliferation to a greater extent than the known SFK inhibitor PP2, shows dose-dependent inhibition of leukemia stem cells (LSCs) proliferation with IC50 <1 uM in 17 of 25 AML cases.
RK-20449 significantly reduces human LSC and non-stem AML burden in vivo models.
