flt3

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

FLT3/ITD-IN-3 (Compound 19) is a potent inhibitor of FLT3-ITD, acting on FLT3D835Y (IC50: 0.3 nM), FLT3 (IC50: 0.4 nM) and FLT3-ITD (IC50: 0.9 nM). FLT3/ITD-IN-3 showed potent inhibition of FLT3 phosphorylation and was effective against the proliferation of AML cells.

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

3-amino-1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]propan-1-one dihydrochloride is used in the synthesis of various compounds.

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].

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].

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).

FLT3-IN-15 is an orally active and potent FLT3 inhibitor, capable of acting on FLT3 (IC50: 0.87 nM) and FLT3/D835Y (IC50: 0.32 nM).

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

FLT3/ITD-IN-1 (Compound 1) is a highly potent inhibitor of FLT3 internal tandem duplications (FLT3-ITD). It exhibits remarkable inhibitory effects against FLT3 and FLT3-ITD, with impressive IC50 values of 38.2 nM and 144.1 nM, respectively. Moreover, FLT3/ITD-IN-1 shows exceptional antiproliferative activities against several acute myeloid leukemia cell lines [1].

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.

FLT3-IN-17 is an FAK inhibitor (IC50: 12 nM). FLT3-IN-17 inhibits the activity of CYPs and FLT3 mutants and has an IC50 of <0.5 nM for D835Y. FLT3-IN-17 can be used in cancer research.

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

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.

FLT3-IN-19 (Comp 50) is a potent, selective inhibitor of FLT3, demonstrating an IC50 value of 0.213 nM, and is applicable in research pertaining to acute myeloid leukemia (AML) [1].

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

FLT3-IN-18, a potent and selective FLT3 inhibitor, exhibits an IC50 value of 0.003 μM. It effectively induces apoptosis and G1 phase cell cycle arrest, while inhibiting FLT3 and STAT5 phosphorylation. This compound holds potential for acute myeloid leukemia (AML) research.

PROTAC FLT3/CDK9 degrader-1, a potent dual degrader of FLT3 and CDK9, effectively induces apoptosis and targets protein degradation of FLT3 and CDK9. This compound holds research potential for FLT3-ITD mutated AML [1].

FLT3-IN-16 exhibits potent inhibitory activity against FLT3 tyrosine kinase with an IC 50 of 1.1 μM. FLT3-IN-16 can be used for researching acute myeloid leukemia [1].

FLT3-IN-13 (compound 20) is a highly effective inhibitor targeting both topoisomerase II and FLT3 proteins in leukemic cells. It exhibits potent activity against these targets, with IC50 values of 2.26 μM for both. Moreover, FLT3-IN-13 induces cell cycle arrest at the G2/M phase and promotes apoptosis. Notably, it displays considerable anticytotoxic activity, specifically against leukemia [1].

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

FLT3/TrKA-IN-1 is a potent FLT3/TrKA dual kinase inhibitor, capable of acting on FLT3 (IC50: 43.8 nM), FLT3-ITD (IC50: 97.2 nM), FLT3-TKD (IC50: 92.5 nM) and TrKA (IC50: 23.6 nM). -FLT3/TrKA-IN-1 has potential for acute myeloid leukaemia (AML) studies.

FLT3/ITD-IN-4 (Compound 16) is a selective inhibitor of FLT3 internal tandem repeat mutations (FLT3-ITD) (IC50: 2.3 nM). FLT3/ITD-IN-4 can be used to study acute myeloid leukaemia.

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

FLT3-IN-6 is a potent and selective inhibitor of FLT3-ITD (FLT3 mutation) with an IC50 of 1.336 nM.

FLT3/D835Y-IN-1 (compound 13a) is a orally active, and selective inhibitor of FLT3 and FLT3/D835Y, with IC50s of 0.26 nM and 0.18 nM, respectively. FLT3/D835Y-IN-1 has anticancer efficacy, and has research value in AML (acute myeloid leukemia).

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.

FLT3-IN-21 (compound LC-3), a potent FLT3 inhibitor with an IC50 value of 8.4 nM, induces apoptosis and arrests the cell cycle in the G1 phase. It 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, demonstrating IC50 values of 1 nM for FLT3-D835Y and 4 nM for FLT3-ITD. It exhibits anti-proliferative effects on FLT3-ITD-positive AML cell lines, with IC50s of 7 nM in MV4-11 and 9 nM in MOLM-13, as well as 4 nM in a MOLM-13 variant harboring the FLT3-ITD-D835Y mutation. FLT3-IN-20 is utilized in cancer research [1].

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.

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.

Flt3 Inhibitor IV is a potent ATP-competitive Flt3 inhibitor.

FLT3/CDK4-IN-1 is a highly selective, potent, orally active dual inhibitor of FLT3/CDK4, acting on FLT3 (IC50: 7 nM) and CDK4 (IC50: 11 nM).FLT3/CDK4-IN-1 has good anti-tumour effects in vivo, showing anti-proliferative effects on some cancer cells.

JAK2/FLT3-IN-1 has anti-cancer activity. JAK2/FLT3-IN-1 is a potent and orally effective dual JAK2/FLT3 (Janus kinase 2/ FMS-like tyrosine kinase 3) inhibitor with IC50 values of 0.7 nM, 4 nM, 26 nM and 39 nM for JAK2, FLT3, JAK1 and JAK3, respectively.

PROTAC FLT-3 degrader 1 is a PROTAC FLT-3 degrader of internal tandem duplication (ITD)(IC50 0.6 nM),with anti-proliferative activity.

MDK5466 is an Flt3 inhibitor that acts by preventing glutamate-induced cell death.

TCS 359 (FLT3 Inhibitor) is a potent FLT3 inhibitor with IC50 of 42 nM.

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

Antiproliferative Against-3 (comp 33) demonstrates significant activity against Hela (IC 50 = 0.21 µM), A549 (IC 50 = 0.39 µM), and MCF-7 (IC 50 = 0.33 µM) cell lines. Additionally, it induces apoptosis in a dose-dependent manner by arresting A549 cells in the G1 phase.

Edicotinib (JNJ-527) is a brain penetrant and orally active inhibitor of the colony-stimulating factor-1 receptor (IC50: 3.2 nM). It shows less inhibitory effects on KIT and FLT3 (IC50: 20 nM and 190 nM). It has the potential for Alzheimer's disease and rheumatoid arthritis treatment.

Pexidartinib (PLX-3397) is a capsule formulation containing a small-molecule receptor tyrosine kinase (RTK) inhibitor of KIT, CSF1R and FLT3 with potential antineoplastic activity.

Sorafenib (Bay 43-9006) is a multikinase inhibitor that inhibits Raf-1, B-Raf, VEGFR2, VEGFR3, VEGFR4, PDGFRβ, FLT3, c-Kit, and others (IC50=6/22/90/15/20/20/57/58 nM) with oral activity. Sorafenib has antitumor activity and can induce autophagy and apoptosis as well as agonistic ferroptosis.

Fedratinib (TG-101348) (TG101348) is an ATP-competitive inhibitor of JAK2 (IC50: 3 nM) with significantly less potent activity against JAK3.

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.

Cabozantinib (XL184) is a multi-targeted tyrosine kinase receptor inhibitor that inhibits VEGFR2, c-Met, Kit, Axl, and Flt3 (IC50=0.035/1.3/4.6/7/11.3 nM). Cabozantinib exhibits both antitumor and antiangiogenic activity.

Gilteritinib (ASP2215) 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.

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.

BPR1J-097, a new-type small molecule FLT-3 inhibitor(IC50=11±7 nM), is with great anti-tumor activities in vivo.

AZ7550 hydrochloride (AZ7550 hydrochloride ), an active metabolite of AZD9291, inhibits the activity of IGF1R (IC50: 1.6 μM).

Cabozantinib hydrochloride (XL184) is a potent pan-tyrosine kinases inhibitor that inhibits VEGFR2, c-Met, Kit, Axl, and Flt4 (IC50s: 0.035, 1.3, 4.6, 7 and 6 nM).