flt3 (itd)

GTP-14564 is a novel tyrosine kinase inhibitor that also inhibits wt-FLT3 and ITD-FLT3. GTP-14564 inhibits the growth of interleukin-3-independent Ba F1 expressing ITD-FLT3 at 3 μ m, whereas a 30-fold higher concentration of GTP-14564 is required to inhibit the FLT3 ligand-dependent growth (wt-FLT3) of Ba F3 expressing wild-type FLT3. F3 expressing wild-type FLT3 (wt-FLT3).

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.

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 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 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.

PDGFRα FLT3-ITD-IN-3 (Compound 18d) is a potent inhibitor of PDGFRα (IC50: 0.153 μM) and FLT3 (IC50: 0.004 μM), with potential applications in the study of acute myeloid leukaemia or chronic eosinophilic leukaemia.

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.

PDGFRα FLT3-ITD-IN-1 are potent inhibitors of PDGFRα FLT3, and their IC50 values are greater than 0.036 and 0.003 μM, respectively. PDGFRα FLT3-ITD-IN-1 exhibits investigational potential in acute myeloid leukemia or chronic eosinophilic leukemia.

PDGFRα FLT3-ITD-IN-2 is a potent inhibitor of PDGFRα (IC50>20 μM) and FLT3 (IC50: 0.004 μM). PDGFRα FLT3-ITD-IN-2 has shown investigational potential in acute myeloid leukemia or chronic eosinophilic leukemia.

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.

Tandutinib (CT53518) (MLN518, CT53518), an effective FLT3 antagonist (IC50: 0.22 μM), can also inhibit c-Kit and PDGFR, 15-20 fold higher potency for FLT3 versus CSF-1R and >100-fold selectivity for the same target versus FGFR, EGFR, and KDR.

Quizartinib (AC220) is an inhibitor of FLT3 (Kd: 1.6 nM) and demonstrates high selectivity for FLT3 when tested against a panel of 227 additional kinases.

HM43239 is an orally active and selective FLT3 inhibitor with IC 50 s of 1.1 nM, 1.8 nM and 1.0 nM for FLT3 WT, FLT3 internal tandem duplication (ITD) and FLT3 D835Y kinases, respectively. HM43239 directly inhibits the kinase activity of FLT3 as a reversible Type I inhibitor and effectively modulates downstream p-STAT5 and p-ERK. HM43239 also demonstrated inhibition of SYK, JAK1 2 and TAK1. HM43239 inhibits the proliferation and induces the apoptosis of leukemic cells [1] [2] [3].

BSc5371 is a potent and irreversible FLT3 inhibitor (Kds: 1.3, 0.83, 1.5, 5.8, and 2.3 nM for mutant FLT3 D835H, FLT3 ITD D835V, FLT3 ITD F691L, FLT3-ITD, and wild type FLT3 wt).

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.

BIX02188 is a selective and potent MEK5 inhibitor that inhibits MEK5-induced apoptosis in cells expressing the oncogenic mutant FLT3-ITD.

SILA-123, an inhibitor of FLT3 (FLT3-WT: IC50=2.1 nM; FLT3-ITD: IC50=1.0 nM), induces cell apoptosis by hindering the cell cycle progression at the G0 G1 phase through the suppression of FLT3 phosphorylation and its downstream signaling pathways. This compound is utilized in the study of acute myeloid leukemia.

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.

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

JH-IX-179 is a novel type I ATP competitive and highly selective FLT3 inhibitor. JH-IX-179 is much more selective for FLT3 and FLT3 mutants than for Kronani. In addition, JH-IX-179 showed little human serum protein binding and effectively inhibited autoph

AC-4-130, a powerful inhibitor of the SH2 domain of STAT5, effectively hinders STAT5 activation, dimerization, nuclear translocation, and transcription of genes reliant on STAT5. This compound directly binds to STAT5, ultimately leading to cell cycle arrest and apoptosis in FLT3-ITD-driven leukemic cells. AC-4-130 exhibits notable anti-cancer properties and effectively suppresses abnormal STAT5 activity in acute myeloid leukemia (AML), making it a promising therapeutic option [1].