FLT3 Inhibitor

FLT3/ITD-IN-2 (Compound 17) is a potent FLT3 internal tandem duplications (FLT3-ITD) inhibitor with IC₅₀ values of 0.3, 0.4 and 1.0 nM against FLT3^D835Y, FLT3 and FLT3-ITD, respectively. FLT3/ITD-IN-2 potently inhibits the phosphorylation of FLT3 and displays excellent antiproliferative activities against acute myeloid leukemia cell lines.

LBW242, a 3-mer and Smac mimetic, is a potent and orally active proapoptotic IAP inhibitor. LBW242 shows effects on mutant FLT3-expressing cells. LBW242 has activity against multiple myeloma, and potentiates TRAIL- and anticancer agent-mediated cell death of ovarian cancer cells.

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.

FLT3-IN-11 (compound 30) is a potent, selective and orally active FLT3 kinase inhibitor with IC₅₀s of 7.22 nM and 4.95 nM for wild-type FLT3 and FLT3-D835Y, respectively. FLT3-IN-11 high selectivity for FLT3 over c-KIT (>1000-fold). FLT3-IN-11has excellent anti-acute myeloid leukemia (AML) activity (MV4-11 cells, IC₅₀ of 3.2 nM).

FLT3-IN-32 TFA is a potent FLT3 inhibitor with an IC₅₀s of 2.40 nM and 3.83 nM against FLT3-ITD and FLT3-D835Y. FLT3-IN-32 TFA inhibits proliferation/survival of human MV4-11 cells with an IC₅₀ of 0.07 nM. FLT3-IN-32 TFA can be used for the study of acute myeloid leukemia (AML).

MolPort-002-705-878 is a highly selective FMS-like tyrosine kinase 3 (FLT3) inhibitor with a binding affinity of −11.33 kcal/mol. MolPort-002-705-878 inhibits the proliferation of FLT3-mutated acute myeloid leukemia (AML) cells. MolPort-002-705-878 is promising for research of FLT3-mutated AML.

FLT3-IN-37 (Compound 6z) is a potent inhibitor of FLT3-ITD, with IC₅₀ values of 1.5 and 3.4 nM for FLT3-ITD and TEL-VEGFR2, respectively. FLT3-IN-37 exhibits high selectivity for wild-type FLT3 (WT) and c-Kit. FLT3-IN-37 inhibits FLT3 phosphorylation and downregulates the expression of p-Akt, p-STAT5, and p-ERK. FLT3-IN-37 exerts anti-leukemia effects by blocking the cell cycle and inducing apoptosis (apoptosis). FLT3-IN-37 can be used for research on acute myeloid leukemia (AML).

LT-540-717 (compound 32) is a potent FLT3 inhibitor (IC₅₀=0.62 nM) with antiproliferative activity. LT-540-717 also inhibits several acquired FLT3 mutations, FLT3 (ITD, D835V), FLT3 (ITD, F691L), FLT3 (D835Y) and FLT3 (D835V). LT-540-717 has potential to be an anti-AML agent.

FLT3-IN-36 is a potent FLT3 inhibitor. FLT3-IN-36 exhibits antitumor activity against FLT3-mutated acute myeloid leukemia (AML) cells. FLT3-IN-36 induces cell cycle arrest, reduces mitochondrial membrane potential, and induces apoptosis, downregulating FLT3 and downstream protein expression (including AKT, ERK, PI3K, and STAT5). FLT3-IN-36 can be used for AML research.

Ki11502 is a multi-targeted receptor tyrosine kinase (RTK) inhibitor that selectively inhibits the activity of PDGF β/α receptors with IC₅₀ values less than 10 nM. Ki11502 selectively inhibits PDGF β receptor phosphorylation, proliferation, and proteoglycan synthesis in human vascular smooth muscle cells. Ki11502 can induce Apoptosis) and exhibits profound antiproliferative effects on select subsets of leukemia, including those with Imatinib (HY-15463) resistant mutations. Ki11502 is highly suitable for studying the role of PDGF in vascular diseases, particularly the role of proteoglycans in atherosclerosis.

c-Met-IN-14 (compound 26af) is a selective inhibitor of c-Met kinase from N-sulfonylamidine-based derivatives, with an IC₅₀ value of 2.89 nM. c-Met-IN-14 shows anticancer activity by blocking phosphorylation of c-Met, and arrests cell cycle at G2/M phase. c-Met-IN-14 induces apoptosis of A549 cells in a dose-dependent manner.

Dovitinib-d₈ is the deuterium labeled Dovitinib. Dovitinib (CHIR-258) is a multi-targeted tyrosine kinase inhibitor with IC₅₀s of 1, 2, 8/9, 10/13/8, 27/210 nM for FLT3, c-Kit, FGFR1/FGFR3, VEGFR1/VEGFR2/VEGFR3 and PDGFRα/PDGFRβ, respectively.

FLT3-ITD-IN-2 (Compound A1) is an inhibitor for FLT3-ITD kinase with an IC₅₀ of 2.12 nM. FLT3-ITD-IN-2 inhibits the proliferation of FLT3-dependent human AML cell line MOLM-13 with an IC₅₀ of 25.65 nM. FLT3-ITD-IN-2 exhibits antitumor efficacy against acute myeloid leukemia.

SILA-123 is a FLT3 inhibitor (FLT3-WT: IC₅₀=2.1 nM; FLT3-ITD: IC₅₀=1.0 nM). SILA-123 inhibits FLT3 phosphorylation and downstream signaling pathways, leading to apoptosis by arresting cell cycle progression at the G0/G1 phase. SILA-123 can be used in the study of acute myeloid leukemia.

Multi-kinase inhibitor 4 (compound 14) is an orally active inhibitor of FLT1, KDR, FLT3, FLT4, PDGFRα, PDGFRβ, with IC₅₀s of 1.97 nM, 1.04 nM, 0.33 nM, 1.44 nM, 0.18 nM, 0.89 nM. Multi-kinase inhibitor 4 plays an important role in cancer research.

JH-IX-179 is an FLT3 inhibitor (IC₅₀ = 4 nM (FLT3-ITD), 10 nM (FLT3-D835Y)). JH-IX-179 inhibits G1 phase arrest and induces apoptosis in FLT3-ITD-expressing cells. JH-IX-179 can be used in acute myeloid leukemia (AML) research.

UNC1666 is an ATP-competitive dual-target Mer/Flt3 tyrosine kinase inhibitor with IC₅₀ values of 0.55 nM and 0.69 nM, and K_i values of 0.16 nM and 0.67 nM, respectively. UNC1666 reduces the phosphorylation levels of Mer and Flt3, suppresses downstream pro-survival signaling pathways (Erk1/2, Akt and Stat), induces cell apoptosis, and decreases colony formation of acute myeloid leukemia cells. UNC1666 is applicable to research related to acute myeloid leukemia.

UNC3133 is an orally active, limitedly selective MerTK inhibitor with an IC₅₀ of 3.0 nM. UNC3133 inhibits Axl, Tyro3 and Flt3 kinases, with IC₅₀ values of 17 nM, 31 nM and 6.8 nM, respectively. UNC3133 is applicable to the research of inflammatory diseases and cancers.

HDAC-IN-63 (Compound 63) is a dual FLT3/HDAC inhibitor (IC₅₀: 0.844 and 30.0 nM for FLT3 and HDAC1 respectively). HDAC-IN-63 inhibits MV4-11 cell proliferation (IC₅₀: 92 nM. HDAC-IN-63 induces apoptosis and arrests cell cycle in MV4-11 cells. HDAC-IN-63 can be used for research of acute myeloid leukemia (AML).

HSN748 is a Ponatinib (HY-12047) analogue and a multikinase inhibitor. HSN748 has inhibitory activity on FLT3, ABL1, RET, PDGFRα/β, MNK1, MNK2 and other kinases. HSN748 can inhibit the growth of chronic myeloid leukemia and acute myeloid leukemia cell lines and can be used in the study of leukemia.