E6201 (ER-806201) is an ATP-competitive dual kinase inhibitor of MEK1 and FLT3. E6201 inhibits MEK1- induced ERK2 phosphorylation with an IC50 value of 5.2 nM, MKK4-induced JNK phosphorylation with an IC50 value of 91 nM, and MKK6-induced p38 MAPK phosphorylation with an IC50 value of 19 nM. Anti-tumor and anti-psoriasis efficacy[1][2].
Zotiraciclib (TG02) is an orally active potent inhibitor of CDK2, JAK2 and FLT3 with IC50 values of 13, 73, and 56 nM, respectively. Zotiraciclib can be used for the research of advanced leukemias and multiple myeloma[1][2].
Gandotinib (LY2784544) is a potent JAK2 inhibitor with IC50 of 3 nM. Gandotinib (LY2784544) also inhibits FLT3, FLT4, FGFR2, TYK2, and TRKB with IC50 of 4, 25, 32, 44, and 95 nM.
Sitravatinib malate (MGCD516 malate) is an orally bioavailable receptor tyrosine kinase (RTK) inhibitor with IC50s of 1.5 nM, 2 nM, 2 nM, 5 nM, 6 nM, 6 nM, 8 nM, 0.5 nM, 29 nM, 5 nM, and 9 nM for Axl, MER, VEGFR3, VEGFR2, VEGFR1, KIT, FLT3, DDR2, DDR1, TRKA, TRKB, respectively[1]. Sitravatinib malate shows potent single-agent antitumor efficacy and enhances the activity of PD-1 blockade through promoting an antitumor immune microenvironment[2].
AMG 925 is a potent, selective, and orally available FLT3/CDK4 dual inhibitor with IC50s of 2±1 nM and 3±1 nM, respectively.
USP10 inhibitor Wu-5 (Wu-5) is a novel small molecule USP10 inhibitor inducing the degradation of FLT3-mutated protein, directly interacts and inactivates USP10, the deubiquitinase for FLT3-ITD in vitro (IC50=8.3 uM) and in FLT3-ITD-positive AML cells.Wu-5 selectively inhibited the viability of FLT3 inhibitor-sensitive (MV4-11, Molm13) and -resistant (MV4-11R) FLT3-ITD-positive AML cells with IC50 of 3.794, 5.056, and 8.386 uM, respectively.Wu-5 (1-10 μM) dose-dependently induced apoptosis of MV4-11, Molm13, and MV4-11R cells through the proteasome-mediated degradation of FLT3-ITD.Combined treatment of Wu-5 and crenolanib produced synergistic cell death in FLT3-ITD-positive cells via the reduction of both FLT3 and AMPKα proteins.
SEL24-B489 (SEL24) is a potent, dual PIM and FLT3-ITD inhibitor with Kd of 2/2/3 nM for PIM1/2/3, Kd of 160/16 nM for FLT3-WT/FLT3-ITD, respectively; exhibits significantly broader on-target activity in AML cell lines (MV-4-11 GI50=20 nM) and primary AML blasts than selective FLT3-ITD or PIM inhibitors, decreases viability of AML cells with FLT3-TKD mutations associated with resistance to selective FLT3-ITD inhibitors; inhibits the growth of a broad panel of AML cell lines in xenograft models. Blood Cancer Phase 2 Clinical
FLT3-IN-1 is a potent FLT3 inhibitor extracted from patent WO2015056683A1, compound example A.
Tyrphostin AG1296 is a potent and selective inhibitor of platelet-derived growth factor receptor (PDGFR), with an IC50 of 0.8 μM. Tyrphostin AG1296 inhibits signaling of human PDGF α- and β-receptors as well as of the related stem cell factor receptor (c-Kit). Tyrphostin AG1296 is also a potent inhibitor of FLT3, with an IC50 in the micromolar range[1][2][3].
HP1328 is a potent inhibitor of FLT3 receptor tyrosine kinase (FLT3/ITD mutation). HP1328 is a benzoimidazole scaffold-based compound. HP1328 significantly reduces the leukemia burden and prolongs the survival of mice with FLT3/ITD leukemia[1].
JNJ-47117096 hydrochloride is potent and selective MELK inhibitor, with an IC50 of 23 nM, also effectively inhibits Flt3, with an IC50 of 18 nM.