flt3-in-4

FLT3-IN-4 (FLT3 inhibitor 9u) is a potent and orally effective Fms-like tyrosine receptor kinase 3 (FLT3; IC50=7 nM) inhibitor ,for treating acute myelogenous leukemia.

IRAK1 4 pan-FLT3 Kinase-IN-1 (Compound 31) is a potent inhibitor of IRAK1, IRAK4, and FLT3 kinases, demonstrating IC50 values of 5 nM for IRAK1, 0.6 nM for IRAK4, and less than 0.5 nM for FLT3. It exhibits favorable pharmacokinetic properties and holds promise for research in acute myeloid leukemia, with survival extension effects comparable to Gilteritinib.

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.

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.

Cediranib (AZD2171) (AZD2171) is a highly potent (IC50 < 1 nmol L) ATP-competitive inhibitor of recombinant KDR tyrosine kinase in vitro, also inhibits Flt1 4 (IC50: 5 nM ≤3 nM), similar activity against PDGFRβ and c-Kit, selective more for VEGFR than PDGFR-α (36-fold), CSF-1R (110-fold), and Flt3 (1000-fold) in HUVEC cells.

HPK1-IN-2 (Thieno[2,3-b]pyridin-6(7H)-one, 4-amino-5-[6-(4-methyl-1-piperazinyl)-1H-benzimidazol-2-yl]-HPK1-IN-2) is a potent and orally active inhibitor of hematopoietic progenitor kinase-1 (HPK1; IC50<0.05 μΜ). It also inhibits Lck (0.05 μΜFlt3 (IC50<0.05 μΜ) kinase activities with antitumor activity.

FLT3-IN-10 (2-Oxazolamine, 5-(4-fluorophenyl)-N-phenyl-) (compound 7c) is a potent inhibitor of FMS-like tyrosine kinase 3 (FLT3). FLT3-IN-10 shows the potential for the treatment of FLT3-mutated acute myeloid leukemia (AML).

JAK2 FLT3-IN-1 (TFA) is an orally active dual inhibitor of JAK2 (IC50: 0.7 nM) and FLT3 (IC50: 4 nM) that demonstrates anticancer effects, also affecting JAK1 (IC50: 26 nM) and JAK3 (IC50: 39 nM).

LY2784544(Gandotinib (LY2784544)) is a potent JAK2 inhibitor (IC50: 3 nM), effective in JAK2V617F(Ki: 0.245 nM). The selectivity is higher 8- and 20-fold than JAK1 and JAK3.

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.

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].

Multi-kinase inhibitor 4 (compound 14) serves as an orally effective inhibitor targeting FLT1, KDR, FLT3, FLT4, PDGFRα, and PDGFRβ, exhibiting IC50 values of 1.97 nM, 1.04 nM, 0.33 nM, 1.44 nM, 0.18 nM, and 0.89 nM respectively. This compound plays a crucial role in cancer research.

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.

TAS05567 is a potent, highly selective, and ATP-competitive Syk inhibitor (IC50: 0.37 nM), showing >70% inhibition of Syk and four other kinases [FLT3 (IC50: 10 nM), JAK2 (IC50: 4.8 nM), KDR (IC50: 600 nM), RET (IC50: 29 nM)] in a panel of 192 kinases.

Flonoltinib maleate is an orally effective dual JAK2 FLT3 inhibitor, with IC50 values of 0.7 nM for JAK2, 4 nM for FLT3, 26 nM for JAK1, and 39 nM for JAK3. Known as JAK2 FLT3-IN-1, it exhibits anticancer activity.

Luxeptinib (CG-806) is a novel pan-FLT3 pan-BTK inhibitor that is administered orally. It exhibits potent and reversible inhibition of these enzymes, acting through a non-covalent mechanism. Luxeptinib effectively induces cell cycle arrest, apoptosis, or autophagy in acute myeloid leukemia cells [1][2][3][4].

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-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].

FGFRs-IN-1 (Compound A16) is an orally active inhibitor targeting FGFR1 2 3 4, with IC50 values of 2.3, 7, 11, and 163 nM respectively. It also inhibits VEGFR1 2 3, Abl, and Flt3, with IC50 values of 61, 176, 112, 26, and 353 nM. The compound shows weak inhibition of CYP enzymes. FGFRs-IN-1 reduces the expression of α-SMA and collagen I, and it inhibits epithelial-mesenchymal transition (EMT) in A549 cells stimulated by TGF-β1. Additionally, FGFRs-IN-1 demonstrates anti-inflammatory activity in mouse models of lung fibrosis induced by Bleomycin and liver fibrosis induced by CCl4.

Gilteritinib-d8 is a deuterated compound of Gilteritinib. Gilteritinib has a CAS number of 1254053-43-4. Gilteritinib is a potent inhibitor at the FMS-related tyrosine kinase 3 (FLT3) and AXL tyrosine kinase receptors (IC50 = 0.29 nM and <1 nM, respectively). In preClinicalal studies, gilteritinib showed strong antileukemic and antitumor effects. Gilteritinib is currently in several Phase 3 Clinicalal trials for acute myeloid leukemia.

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].

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].