flt3 (d835y)

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

Amuvatinib (MP470) is an orally bioavailable synthetic carbothioamide with potential antineoplastic activity.

KW-2449 is a multiple-targeted inhibitor, mostly for Flt3 (IC50: 6.6 nM), modestly effective to Bcr-Abl, FGFR1, and Aurora A; little inhibitory on PDGFRβ, IGF-1R, EGFR.

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).

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.

Abemaciclib methanesulfonate (LY2835219) is a specific and effective inhibitor of CDK4(IC50=2 nM) and CDK6(IC50=10 nM).

Abemaciclib (LY2835219) is a dual inhibitor of CDK4 6 (IC50=2 10 nM) with selectivity and specificity. Abemaciclib has antitumor activity and is used to treat advanced or metastatic breast cancer.

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.

Pacritinib (SB1518) citrate effectively inhibits wild-type JAK2 (IC 50 =23 nM) and the JAK2 V617F mutant (IC 50 =19 nM). It also targets FLT3 (IC 50 =22 nM) and the FLT3 D835Y mutant (IC 50 =6 nM). This compound is utilized in the study of acute myeloid leukemia (AML) and myelofibrosis (MF) [1] [2] [3].

G-749 hydrochloride is a novel FLT3 inhibitor that showed potent and sustained inhibition of the FLT3 wild type and mutants including FLT3-ITD, FLT3-D835Y, FLT3-ITD N676D, and FLT3-ITD F691L in cellular assays.

CCT241736 is an orally bioavailable dual FLT3 Aurora kinase inhibitor that also inhibits clinically relevant FLT3-resistant mutants including FLT3-ITD and FLT3, CCT241736, an advanced analog of CCT137690, is a preclinical development candidate for the treatment of human malignancies, and in particular AML in adults and children.

BPR1J-097) is a novel FLT-3 inhibitor(IC50: 11±7 nM) with promising in vivo anti-tumor activities. It also inhibits FLT-3 D835Y (IC50: 3 nM).

FLT3-IN-11 (compound 30) is an orally active, potent, and selective inhibitor of FLT3 kinase that targets wild-type FLT3 (IC50: 7.22 nM) and FLT3-D835Y (IC50: 4.95 nM), demonstrating significant anti-AML effects with an IC50 value of 3.2 nM for MV4-11 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.

G-749, a new-type FLT3 inhibitor, exhibits effective and sustained inhibition of the FLT3 wild type and mutants.

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-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.

LT-540-717 (compound 32), a potent FLT3 inhibitor (IC50=0.62 nM), exhibits antiproliferative activity and effectively inhibits various acquired FLT3 mutations, including FLT3 (ITD, D835V), FLT3 (ITD, F691L), FLT3 (D835Y), and FLT3 (D835V), indicating its potential as an anti-AML agent [1].

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.

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

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].

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].