flt 3

FLT3-IN-10 (2-Oxazolamine, 5-(4-fluorophenyl)-N-phenyl-) (compound 7c) is a potent inhibitor of FMS-like tyrosine kinase 3 (FLT3). FLT3-IN-10 shows the potential for the treatment of FLT3-mutated acute myeloid leukemia (AML).

FLT3-IN-3 is an effective FLT3 inhibitor, and the IC50s of FLT3 WT and FLT3 D835Y are 13 and 8 nM, respectively.

FLT3-IN-2 is an FLT3 inhibitor (IC50<1 μM).

FLT3-IN-4 (FLT3 inhibitor 9u) is a potent and orally effective Fms-like tyrosine receptor kinase 3 (FLT3; IC50=7 nM) inhibitor ,for treating acute myelogenous leukemia.

SKLB4771 (FLT3-IN-1) is a novel potent and selective Flt3 inhibitor.

CHMFL-FLT3-122 is a potent and orally available FLT3 kinase inhibitor used to treat FLT3-ITD positive acute myeloid leukemia. CHMFL-FLT3-122 significantly suppressed the tumor growth in MV4-11 cell inoculated xenograft model (50 mg/kg) without exhibiting obvious toxicity in vivo.

FLT3-IN-16 exhibits potent inhibitory activity against FLT3 tyrosine kinase with an IC 50 of 1.1 μM. FLT3-IN-16 can be used for researching acute myeloid leukemia [1].

FLT3-IN-6 is a potent and selective inhibitor of FLT3-ITD [FLT3 mutation], with an IC50 of 1.336 nM.

PROTAC FLT-3 degrader 1 is a PROTAC FLT-3 degrader of internal tandem duplication (ITD) with an IC50 of 0.6 nM and exhibits anti-proliferative activity.

FLT3 ligand-2 serves as a ligand for the target protein in PROTAC. It is utilized for synthesizing PROTAC FLT-3 degrader 1.

FLT3-ITD-IN-2 (Compound A1) is an inhibitor of the FLT3-ITD kinase, exhibiting an IC50 of 2.12 nM. It effectively suppresses the proliferation of the FLT3-dependent human AML cell line MOLM-13, with an IC50 of 25.65 nM. FLT3-ITD-IN-2 demonstrates antitumor activity against acute myeloid leukemia.

IRAK1/4/pan-FLT3 Kinase-IN-1 (Compound 31) is a potent inhibitor of IRAK1, IRAK4, and FLT3 kinases, demonstrating IC50 values of 5 nM for IRAK1, 0.6 nM for IRAK4, and less than 0.5 nM for FLT3. It exhibits favorable pharmacokinetic properties and holds promise for research in acute myeloid leukemia, with survival extension effects comparable to Gilteritinib.

FLT3 Ligand-Linker Conjugate 1 consists of an FLT3 ligand and a PROTAC linker that can recruit E3 ligase VHL. This conjugate is useful for synthesizing PROTAC RSS0680, a bifunctional compound designed for targeted protein degradation of kinases.

FLT3-IN-29 (Compound MY-10) is an FLT3 inhibitor with IC50 values of 6.5 nM and 10.3 nM for FLT3-ITD and FLT3-D835Y mutants, respectively. It induces cell cycle arrest at the G0/G1 phase and effectively triggers apoptosis (Apoptosis). Additionally, FLT3-IN-29 reduces reactive oxygen species (ROS) and mitochondrial membrane potential (MMP), displaying anti-leukemic properties.

FLT3-IN-28 (Compound 12y) is an orally active FLT3 inhibitor with antitumor properties. It selectively targets cancer cells with FLT3 internal tandem duplication (ITD) mutations, demonstrating IC50 values of 85, 290, 130, 65, and 220 nM against BaF3-FLT3-ITD, BaF3-TEL-VEGFR2, MV4-11, MOLM-13, and MOLM-14 cell lines, respectively. These lines include acute myeloid leukemia (AML) cells harboring FLT3-ITD mutations such as MV4-11 and MOLM-13/14. The compound also reduces phosphorylation levels of FLT3 and STAT5 in MOLM-13 cells, leading to cell cycle arrest and apoptosis. With an oral bioavailability of 19.2% in SD rats, FLT3-IN-28 extends survival in a dose-dependent manner in MOLM-13 xenografted NSG mouse models. It holds promise for research in FLT3-ITD-related cancer studies.

FLT3/VEGFR2-IN-1 (Compound 26) is a potent inhibitor of FLT3, VEGFR2, and HDAC, exhibiting IC50 values of 14.5 nM, 3.9 nM, and 30.8 nM against FLT3, VEGFR2, and HDAC1, respectively. It effectively inhibits the phosphorylation of STAT3 and ERK1/2, as well as the proliferation of leukemia cells. FLT3/VEGFR2-IN-1 demonstrates antitumor activity and is applicable in research on acute myeloid leukemia.

FLT3-ITD-IN-3 (13v) is an orally active inhibitor of FLT3-ITD (internal tandem duplication of FLT3), which works by blocking FLT3 signaling. This inhibition leads to cell cycle arrest in the G0/G1 phase and induces apoptosis. The compound is currently employed in studies related to acute myeloid leukemia (AML).

IRAK1/4/pan-FLT3 Kinase-IN-2 (compound 27) is a potent dual inhibitor of IRAK1/4 and FLT3 with IC50 values of 10 nM, 0.7 nM, and < 0.5 nM, respectively. This compound enhances survival in mice models of acute myeloid leukemia.

FLT3-IN-25 (compound 17) is a potent FLT3 inhibitor, demonstrating IC50 values of 1.2 nM for FLT3-WT, 1.4 nM for FLT3-D835Y, and 1.1 nM for FLT3-ITD. This compound plays a significant role in the treatment of acute myeloid leukemia (AML).

FLT3-IN-24 (compound 24) is a potent and selective inhibitor of FLT3 kinase, with an IC50 of 7.94 nM. It also exhibits anti-proliferative effects on cells.

FLT3/CHK1-IN-2 (Compound 30) is a dual inhibitor targeting FLT3 and CHK1, with IC50 values of 25.63 nM for CHK1, 16.39 nM for FLT3-WT, and 22.80 nM for FLT-D835Y. It displays favorable oral pharmacokinetic properties and kinase selectivity. FLT3/CHK1-IN-2 is applicable in acute myeloid leukemia (AML) research.

FLT3-ITD/D835Y-IN-1 (Compound 1) is an inhibitor of FLT3-ITD and BCR-ABL. It induces pro-apoptotic (apoptosis) effects by inhibiting the FLT3 and BCR-ABL pathways, along with potentially other targets. This compound is applicable in acute myeloid leukemia (AML) research.

PROTACFLT3/CDKs degrader-1 (Compound C3) is an agent that degrades cyclin-dependent kinase (CDK2 with a DC50 of 18.73 nM) and FMS-like tyrosine kinase 3 (FLT3). It induces differentiation in HL-60 cells, achieving a 72.77% differentiation rate at 6.25 nM, and inhibits proliferation of acute myeloid leukemia (AML) cells, with an IC50 ranging from 2.9 to 37 nM. PROTACFLT3/CDKs degrader-1 demonstrates potential for improving the treatment of AML.

FLT3-IN-32 is a potent FLT3 inhibitor with high selectivity, effectively suppressing FLT3 activating mutations and inducing apoptosis. It demonstrates good tolerance in non-tumor-bearing mice. In NOD/SCID mice loaded with MV4-11 cells, FLT3-IN-32 exhibits outstanding antitumor efficacy, significantly extending mouse survival. FLT3-IN-32 is applicable for acute myeloid leukemia research.