flt3 (wt)

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).

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.

JAK3-IN-14 is a potent, selective and orally active FLT3 inhibitor, with IC50s of ∼40, 8, and 4 nM for FLT3-WT, FLT3-D835Y, and FLT3-D835H, respectively.

JI6 (JAK3 Inhibitor VI) is a potent, selective and orally active FLT3 inhibitor. JI6 exhibits IC50s of ∼40, 8, and 4 nM for FLT3-WT, FLT3-D835Y, and FLT3-D835H, respectively. JI6 also inhibits c-Kit and JAK3, with IC50s of ∼500 and ∼250 nM, respectively. JI6 has research value in acute myeloid leukemia.

Pacritinib (SB1518) (SB1518) is an effective and specific inhibitor of JAK2 and FLT3 (IC50: 23 22 nM, in cell-free assays).

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].

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

DCC-2036 (Rebastinib (DCC-2036)) is a conformational control Bcr-Abl inhibitor for Abl1(WT, IC50: 0.8 nM) and Abl1(T315I, IC50: 4 nM), also inhibits LYN, SRC, HCK, FGR, FLT3, KDR, and Tie-2, and low activity to c-Kit. Rebastinib aimed at the Angiopoietin2-Tie2 pathway.

FI-700 is a novel and potent FLT3 inhibitor with promising antileukemia activity. FI-700 showed a potent IC(50) value against FLT3 kinase at 20 nmol L in an in vitro kinase assay. FI-700 showed selective growth inhibition against mutant FLT3-expressing leukemia cell lines and primary acute myeloid leukemia cells, whereas it did not affect the FLT3 ligand (FL)-driven growth of Wt-FLT3-expressing cells. Oral administration of FI-700 induced the regression of tumors in a s.c. tumor xenograft model and increased the survival of mice in an i.v. transplanted model. Furthermore, FI-700 treatment eradicated FLT3 ITD-expressing leukemia cells, both in the peripheral blood and in the bone marrow. (Source: Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4575-82.)

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.

JAK3-IN-1 is an orally active, selective and potent JAK3 inhibitor that can be used to study immune system diseases.

FLT3-IN-12 is a selective, potent, orally active FLT3 kinase inhibitor that acts on FLT3-WT (IC50: 1.48 nM) and FLT3-D835Y (IC50: 2.87 nM). FLT3-IN-12 is more selective than c-KIT (>1000-fold). FLT3-IN-12 showed significant anti-AML effects, with an IC50 value of 0.75 nM for MV4-11 cells.

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).

Antiproliferative Agent-34 (Compound A14), a multitarget kinase inhibitor, demonstrates IC50 values of 177 nM for EGFR L858R T790M and 1567 nM for EGFR WT. Additionally, it inhibits JAK2, ROS1, FLT3, FLT4, and PDGFRα with respective IC50s of 30.93 nM, 106.90 nM, 108.00 nM, 226.60 nM, and 42.53 nM. In normoxic conditions, it suppresses the proliferation of H1975 and HCC827 cells with IC50 values below 40 nM, while under hypoxic conditions, its potency increases 4-6 fold, yielding IC50 values less than 10 nM [1].

FLT3-IN-14 is a potent inhibitor of FLT3, targeting FLT3-WT (IC50: 5.6 nM) and FLT3-ITD (IC50: 1.4 nM). It inhibits FLT3 (Y591) phosphorylation, arrests the cell cycle in the G1 phase, and induces apoptosis.

RET-IN-4 is a highly effective and specific RET inhibitor that can be administered orally. It demonstrates remarkable potency, with IC50 values of 1.29 nM, 1.97 nM, and 0.99 nM for inhibiting RET variants including RET (WT), RET (V804M), and RET (M918T), respectively. Moreover, RET-IN-4 exhibits superior selectivity towards kinases JAK2 (IC50 of 4.4 nM) and FLT3 (IC50 of 30.8 nM). Additionally, RET-IN-4 possesses pronounced anticancer properties.

Tuspetinib (HM43239) hydrate is a selectively active FLT3 inhibitor for oral administration, demonstrating IC₅₀ values of 1.1 nM for FLT3 WT, 1.8 nM for FLT3 internal tandem duplication (ITD), and 1.0 nM for FLT3 D835Y kinases. As a reversible type I inhibitor, it suppresses FLT3 kinase activity and influences signaling pathways including p-STAT5, p-ERK, SYK, JAK1 2, and TAK1. Additionally, Tuspetinib hydrate inhibits leukemic cell proliferation and triggers apoptosis [1] [2] [3].