flt-3-in-2

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

FLT3-IN-27 (compound 49) is an inhibitor of FLT3-ITD with an IC50 of 174 nM. It impedes cell growth by causing cell cycle arrest at the G1 phase, making it suitable for research in acute myeloid leukemia.

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-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-IN-21 (compound LC-3), a potent FLT3 inhibitor with an IC50 value of 8.4 nM, induces apoptosis, arrests the cell cycle in the G1 phase, and effectively inhibits the proliferation of FLT3-ITD-positive AML cells MV-4-11 with an IC50 of 5.3 nM. In murine models, a daily dose of 10 mg/kg FLT3-IN-21 markedly inhibited tumor growth in the MV-4-11 xenograft model, achieving a tumor growth inhibition (TGI) of 92.16% [1].

FLT3-IN-22 (compound 22f) is a potent FLT3 inhibitor with IC50 values of 0.941 nM for FLT3 and 0.199 nM for the FLT3/D835Y mutant. It demonstrates significant antiproliferative effects against MV4-11 cells and Ba/F3 cell lines expressing mutant FLT kinase variants, including FLT-D835Y and FLT3-F691L [1].

FLT3-IN-20 (compound 34f) is a potent FLT3 inhibitor with IC50 values of 1 nM for FLT3-D835Y and 4 nM for FLT3-ITD. It shows anti-proliferative effects on FLT3-ITD-positive AML cell lines, with IC50s of 7 nM in MV4-11, 9 nM in MOLM-13, and 4 nM in a MOLM-13 variant harboring the FLT3-ITD-D835Y mutation. FLT3-IN-20 is utilized in cancer research [1].

FLT3-IN-23 (compound 15), a potent inhibitor of FMS-like tyrosine kinase 3 (FLT3), exhibits an IC 50 value of 7.42 nM and demonstrates antiproliferative effects against BaF3 cells harboring diverse FLT3-TKD and FLT3-ITD-TKD mutations [1].

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

OSI-930, an orally active inhibitor of c-Kit and the vascular endothelial growth factor receptor-2 (VEGFR-2), targets cancer cell proliferation and blood vessel growth (angiogenesis) in tumors.

LY2457546 is a potent and orally bioavailable inhibitor of multiple receptor tyrosine kinases involved in angiogenic and tumorigenic signalling. LY2457546 demonstrates potent activity against targets that include VEGFR2 (KDR), PDGFRβ, FLT-3, Tie-2 and members of the Eph family of receptors. In vivo, LY2457546 inhibited VEGF-driven autophosphorylation of lung KDR in the mouse and rat in a dose and concentration dependent manner. LY2457546 was well tolerated and exhibited efficacy in a 13762 syngeneic rat mammary tumor models. Additionally, LY2457546 caused complete regression of well-established tumors in an acute myelogenous leukemia (AML) FLT3-ITD mutant xenograft tumor model. The unique spectrum of target activity, potent in vivo anti-tumor efficacy in a variety of rodent and human solid tumor models, exquisite potency against a clinically relevant model of AML, and non-clinical safety profile justify the advancement of LY2457546 into clinical testing. (source: Invest New D......