FLT3 IN 3

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

FLT3/HDAC-IN-1 is a dual inhibitor targeting FLT3 and HDAC, with IC50 values of 30.4 nM for FLT3 and 52.4, 14.7 nM for HDAC1/3, respectively. It induces apoptosis in MV-4-11 cells and exhibits antiproliferative effects against BaF3 cells transformed by FLT3 mutations. FLT3/HDAC-IN-1 is useful for research on refractory solid tumors and hematological malignancies.

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

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.

PROTACFLT3/GSPT1/IKZF1/3 degrader-1 is an FLT3 PROTAC degrader with DC50 = 1.2 nM. It functions as a molecular glue to degrade its brain substrates and exhibits antiproliferative activity against resistant acute myeloid leukemia (AML) cells, showing potential applications in AML research.

Flt3 Inhibitor IV is a potent ATP-competitive Flt3 inhibitor.

FLT3/ITD-IN-3 (Compound 19) is a potent inhibitor of FLT3-ITD, demonstrating efficacy against FLT3D835Y (IC50: 0.3 nM), FLT3 (IC50: 0.4 nM), and FLT3-ITD (IC50: 0.9 nM). It significantly inhibits FLT3 phosphorylation and effectively suppresses the proliferation of AML cells.

FLT3/CDKs ligand-1 (Compound 14) functions as a ligand for target proteins, promoting the degradation of Cyclin-Dependent Kinases (CDK) and FMS-like tyrosine kinase 3 (FLT3), thereby inhibiting the proliferation and survival of leukemia cells associated with FLT3/CDK. This compound is also used in the synthesis of PROTAC FLT3/CDKs Degrader-1.

Compound 25h, also known as FLT3/HDAC-IN-2, is a dual inhibitor of FLT3/HDAC. It exhibits antiproliferative activity against MOLM-13 cells and is used in the study of acute myeloid leukemia.

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/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/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/IRAK4-IN-1 is a selective inhibitor of FLT3 and IRAK4, exhibiting significant activity against FLT3-WT (IC50= 1.95 nM), FLT3-D835Y (IC50= 3.22 nM), and IRAK4 (IC50= 53.72 nM). It demonstrates low cytotoxicity towards normal bone marrow cells, effectively promotes apoptosis, and has potential to overcome resistance. FLT3/IRAK4-IN-1 can be utilized in studies of acute myeloid leukemia (AML).

PROTACFLT3/JAK2/BRD4 Degrader-1 is a PROTAC degrader targeting FLT3, JAK2, and BRD4, with DC50 values of 5.23 nM, 0.678 nM, and 1.17 nM, respectively. It exhibits potent antiproliferative activity against MV4;11 cells (IC50= 0.79 nM) and FLT3-mutated Ba/F3 cells. Additionally, PROTACFLT3/JAK2/BRD4 Degrader-1 induces apoptosis in MV4;11 cells and demonstrates significant antitumor efficacy in an MV4;11 xenograft model established in NOD SCID mice. This compound is applicable for research in acute myeloid leukemia (AML).

3-amino-1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]propan-1-one dihydrochloride is used in the synthesis of various compounds.

FLT3/ITD-IN-1 (Compound 1) is a highly potent inhibitor of FLT3 internal tandem duplications (FLT3-ITD) with IC50 values of 38.2 nM for FLT3 and 144.1 nM for FLT3-ITD, and shows exceptional antiproliferative activities against several acute myeloid leukemia cell lines [1].

FLT3/D835Y-IN-1 (compound 13a) is an orally active, selective inhibitor of FLT3 and FLT3/D835Y with IC50 values of 0.26 nM and 0.18 nM, respectively. It exhibits anticancer efficacy and has research value in AML (acute myeloid leukemia).

FLT3/TrKA-IN-1 is a potent dual kinase inhibitor that targets FLT3 (IC50: 43.8 nM), FLT3-ITD (IC50: 97.2 nM), FLT3-TKD (IC50: 92.5 nM), and TrKA (IC50: 23.6 nM). FLT3/TrKA-IN-1 shows potential for acute myeloid leukaemia (AML) studies.

FLT3/ITD-IN-4 (Compound 16) is a selective inhibitor of FLT3 internal tandem repeat mutations (FLT3-ITD) with an IC50 of 2.3 nM and is applicable for studying acute myeloid leukemia.

FLT3/CDK4-IN-1 is a highly selective, potent, orally active dual inhibitor of FLT3 (IC50: 7 nM) and CDK4 (IC50: 11 nM), demonstrating significant anti-tumor effects in vivo and anti-proliferative effects on certain cancer cells.

FLT3/ITD-IN-2 is a potent inhibitor of FLT3-ITD and is able to act on FLT3D835Y (IC50: 0.3 nM), FLT3 (IC50: 0.4 nM) and FLT3-ITD (IC50: 1.0 nM).FLT3/ITD-IN-2 effectively inhibits the phosphorylation of FLT3 and is able to effectively inhibit the proliferation of acute myeloid leukemia cells.

PROTAC FLT3/CDK9 degrader-1, a potent dual degrader of FLT3 and CDK9, effectively induces apoptosis and targets protein degradation of FLT3 and CDK9. This compound holds research potential for FLT3-ITD mutated AML [1].

Compound 18, also known as FLT3/CHK-IN-1, is a dual inhibitor targeting FLT3 and CHK1, exhibiting over 1700-fold selectivity towards c-KIT and significantly diminishing hERG affinity, with an IC50 of 58.4 μM. It demonstrates efficacy in suppressing tumor growth in mouse xenotransplantation models implanted with MV-4-11 cells [1].

FLT3/ITD-IN-5 (Example 6) is an orally active inhibitor of both FLT3 and FLT3-ITD, exhibiting IC50 values of 0.088 nM and 0.348 nM, respectively. This compound is utilized in cancer research.