fms-like

Sorafenib (Bay 43-9006) is a multikinase inhibitor that targets 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. It exhibits antitumor properties and can induce autophagy, apoptosis, and agonistic iron death.

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 of FMS-related tyrosine kinase 3 (FLT3) and AXL tyrosine kinase receptors (IC50 = 0.29 nM and <1 nM, respectively). In preclinical studies, gilteritinib demonstrated strong antileukemic and antitumor effects. Gilteritinib is currently in several Phase 3 clinical trials for acute myeloid leukemia.

Sorafenib tosylate (Bay 43-9006) is a potent multikinase inhibitor (IC50s: 6/20/22 nM for Raf-1/VEGFR-3/B-Raf).

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).

4SC-203 is a multikinase inhibitor with potential antineoplastic activity. 4SC-203 selectively inhibits FMS-related tyrosine kinase 3 (FLT3/STK1), FLT3 mutated forms, and vascular endothelial growth factor receptors (VEGFRs).

AKN-028 is an orally active and potent FLT3 tyrosine kinase inhibitor ( IC 50 = 6 nM). AKN-028 causes dose-dependent inhibition of FLT3 autophosphorylation.

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

AST 487 (NVP-AST 487) is a RET kinase inhibitor, inhibiting RET autophosphorylation and activation of downstream effectors. It also can inhibit Flt-3.

SB1317 (TG02) is a potent inhibitor of cyclin dependant kinases (CDKs), Janus kinase 2 (JAK2), and Fms-like tyrosine kinase-3 (FLT3).

AT9283 (J-504568) is an effective multi-targeted inhibitor of JAK2(IC50=1.2 nM) and JAK3(IC50=1.1 nM), Aurora A, Aurora B and Abl(T315I).

R406 (R-406 besylate) is an effective Syk inhibitor (IC50: 41 nM) and shows no effects on Lyn.

Crenolanib (ARO 002) is an orally bioavailable type III tyrosine kinases inhibitor of PDGFRα β and FLT3 (IC50s: 11, 3.2, and 4 nM).

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.

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

Sitravatinib (MGCD516) is an inhibitor targeting multiple RTKs involved in driving sarcoma cell growth, including c-Met, c-Kit, PDGFRα β, PDGFR, and Axl.

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

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.

AMG 925 is a potent and orally bioavailable dual FLT3/CDK4 inhibitor with IC50 of 1 nM and 3 nM, respectively.

ATH686 is an potent and selective Inhibitor of FLT3.

KG5 is a dual allosteric inhibitor of PDGFRβ and B-Raf with a Kd of 520 nM and 300 nM for PDGFRβ and PDGFRα. KG5 inhibits FLT3, KIT, and c-Raf with anticancer and antiangiogenic activities.

CHIR-124 is an effective Chk1 inhibitor (IC50: 0.3 nM). It has 2, 000-fold selectivity against Chk2, 500- to 5, 000-fold less activity against Cdc2 and CDK2/4.

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

Dovitinib (CHIR-258) (TKI258, CHIR258) is a multitargeted RTK inhibitor, mostly for class III (FLT3 c-Kit, IC50: 1 2 nM), also effective to class IV (FGFR1 3) and class V (VEGFR1-4) RTKs (IC50: 8-13 nM), less potent to EGFR, InsR, EphA2, c-Met, IGF-1R, Tie2, and HER2.

Tyrphostin AG1296 (Tyrphostin AG 1296) is an inhibitor of PDGFR with IC50 of 0.3-0.5 μM, no activity to EGFR.

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).

Altiratinib (DCC-2701)(DCC-2701) is a novel c-MET/TIE-2/VEGFR inhibitor; effectively reduce tumor burden in vivo and block c-MET pTyr(1349)-mediated signaling, cell growth and migration as compared with an HGF antagonist in vitro.

AZD2932 is a potent, multi-targeted kinase inhibitor of VEGFR2, PDGFβ, Flt-3, and c-Kit.

5'-Fluoroindirubinoxime (5'-FIO) is a potent FLT3 inhibitor( IC50 : 15 nM).

ENMD-2076, a multi-targeted kinase inhibitor, has specific activity against Aurora A, Flt3, KDR/VEGFR2, Flt4/VEGFR3, FGFR1, FGFR2, Src, PDGFRα.

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).

It is a tyrosine kinase inhibitor.

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

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.

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

UNC2025 (mrx-6313)(IC50 of 0.74 nM and 0.8 nM) is a potent and orally bioavailable dual MER FLT3 inhibitor. UNC-2025 is about 20-fold selectivity higher than Axl and Tyro3.

Linifanib (AL-39324) (ABT-869) is a novel, potent ATP-competitive VEGFR/PDGFR inhibitor for KDR (IC50: 4 nM), CSF-1R (IC50: 3 nM), Flt-1/3 (IC50: 3/4 nM) and PDGFRβ (IC50: 66 nM). Linifanib may exhibit potent antiproliferative and apoptotic effects on tumor cells whose proliferation is dependent on mutant kinases, such as FMS-related tyrosine kinase receptor-3 (FLT3).

AC710 is a potent PDGFR inhibitor with Kds of 0.6 nM for FLT3, 1 nM for KIT, 1.57 nM for CSF1R, 1.3 nM for PDGFRα, and 1 nM for PDGFRβ.

R406 free base (R406 (free base)) is a potent Syk inhibitor.

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.

TG101209 is a selective JAK2 inhibitor with an IC50 of 6 nM.

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].

Lestaurtinib (CEP 701) is an orally available and selective inhibitor of FMS-like tyrosine kinase-3 (FLT3, IC50: 0.9 nM), which inhibits FLT3 autophosphorylation in vitro.Lestaurtinib promotes the expression of c-MYC, inhibits the phosphorylation of RPTKs, and has high affinity for TrkA and JAK2. Lestaurtinib promotes c-MYC expression, inhibits phosphorylation of RPTKs, has a high affinity for TrkA and JAK2, induces apoptosis and cell growth arrest, and can be used to study leukemia.

Fostamatinib Disodium (R788 Disodium) is an orally available Syk kinase inhibitor with potential anti-inflammatory and immunomodulatory activities.

FN-1501 is a potent FLT3 and CDK inhibitor (IC50s: 2.47, 0.85, 1.96, and 0.28 nM for CDK2/cyclin A, CDK4/cyclin D1, CDK6/cyclin D1 and FLT3, respectively). FN-1501 also has anticancer activity.

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.

PKC412(Midostaurin (PKC412); CGP41231; CGP41251) is a broad spectrum protein kinase inhibitor. Midostaurin inhibits protein kinase C alpha (PKCalpha), vascular endothelial growth factor receptor 2 (VEGFR2), c-kit, platelet-derived growth factor receptor (PDGFR) and FMS-like tyrosine kinase 3 (FLT3) tyrosine kinases, which may result in disruption of the cell cycle, inhibition of proliferation, apoptosis, and inhibition of angiogenesis in susceptible tumors.

Dovitinib lactate (TKI-258 lactate)(TKI258) lactate is a potent inhibitor of fibroblast growth factor receptor 3 (FGFR3) (IC50 :5 nM).

Fostamatinib (R788)(IC50 of 41 nM), which is a prodrug of the active metabolite R406, is a Syk inhibitor. It does not work on Lyn.

3-Hydroxy Midostaurin-D5 (CGP52421-D5) is a deuterium-labeled 3-Hydroxy Midostaurin which is a metabolite of PKC412. PKC412 effectively inhibits FMS-like tyrosine kinase-3 (FLT3) autophosphorylation (IC50s: 132 nM and 9.8 μM in culture medium and plasma).

Quizartinib, also know as AC220 and AC010220, is an orally available FLT3 / STK1 inhibitor with potential antineoplastic activity. Class III receptor tyrosine kinase inhibitor AC220 selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/FMS), stem cell factor receptor (SCFR/KIT), and platelet derived growth factor receptors (PDGFRs), resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis. Mutations in FLT3, resulting in constitutive activation, are the most frequent genetic alterations in acute myeloid leukemia (AML) and occur in approximately one-third of AML cases.

(S)-3-Hydroxy Midostaurin is a potent inhibitor of kinases(IC50 of <400 nM for 13 kinases (VEGFR-2, TRK-A, FLT3, et)).

(R)-3-Hydroxy Midostaurin is a potent inhibitor of kinases,is a major metabolite of midostaurin undergoing by the hepatic CYP3A4 enzyme,has the potential for acute myeloid leukemia (AML).

3-Hydroxy Midostaurin (CGP 52421), a PKC412 metabolite, inhibits FMS-like tyrosine kinase-3 (FLT3) autophosphorylation with IC50 values of approximately 132 nM in culture medium and 9.8 μM in plasma. Although less selective, it shows greater cytotoxicity compared to PKC412[1].

Iso-guanosine derivative