Amuvatinib (MP-470) is a potent and multi-targeted inhibitor of c-Kit, PDGFRα and Flt3 with IC50 of 10 nM, 40 nM and 81 nM, respectively.IC50 Value: 10 nM(c-KitD816H); 40 nM(PDGFRαV561D); 81 nM(Flt3D835Y) [1]Target: c-Kit; PDGFRα; FLT3in vitro: The hydrochloride salt of MP-470 also inhibits several mutants of c-Kit, including c-KitD816V, c-KitD816H, c-KitV560G, and c-KitV654A, as well as a Flt3 mutant (Flt3D835Y) and two PDGFRα mutants (PDGFRαV561D and PDGFRαD842V), with IC50 of 10 nM to 8.4 μM. MP-470 potently inhibits the proliferation of OVCAR-3, A549, NCI-H647, DMS-153, and DMS-114 cells, with IC50 of 0.9 μM–7.86 μM [1]. MP-470 also inhibits c-Kit and PDGFRα, with IC50 values of 31 μM and 27 μM, respectively. MP-470 demonstrates potent cytotoxicity against MiaPaCa-2, PANC-1, and GIST882 cells, with IC50 of 1.6 μM to 3.0 μM. MP-470 also binds to and inhibits several c-Kit mutants, including c-KitK642E, c-KitD816V, and c-KitK642E/D816V [2]. In MDA-MB-231 cells, MP-470 (1 μM) inhibits tyrosine phosphorylation of AXL [3]. In LNCaP and PC-3, but not DU145 cells, MP-470 exhibits cytotoxicity with IC50 of 4 μM and 8 μM, respectively, and induces apoptosis at 10 μM. In LNCaP cells, MP-470 (10 μM) elicits G1 arrest and decreases phosphorylation of Akt and ERK1/2 [4].in vivo: In mice xenograft models of HT-29, A549, and SB-CL2 cells, MP-470 (10 mg/kg–75 mg/kg via i.p. or 50 mg/kg–200 mg/kg via p.o.) inhibits tumor growth [1]. In mice bearing LNCaP xenograft, MP-470 (20 mg/kg) combined with Erlotinib significantly induces tumor growth inhibition (TGI) [4].
FLT3-IN-15 is a highly potent and orally active FLT3 inhibitor with IC50s of 0.87 nM and 0.32 nM for FLT3 and FLT3/D835Y, respectively. FLT3-IN-15 can be used for researching acute myeloid leukemia[1].
Antiproliferative agent-30 (Compound 8g) inhibits tubulin assembly and inhibits FLT3 and Abl1. Antiproliferative agent-30 has vascular-disrupting activity. Antiproliferative agent-30 has broad antiproliferative activities against cancer cell lines (IC50s: 0.054 nM, 0.008 nM, 0.144 nM for HCT-116, K562, MV-4-11 cells respectively). Antiproliferative agent-30 also has anticancer effect against AML with FLT3-ITD-TKD mutation[1].
Rebastinib (DCC-2036) is a conformational control Bcr-Abl inhibitor for Abl1WT and Abl1T315I with IC50 of 0.8 nM and 4 nM, also inhibits SRC, KDR, FLT3, and Tie-2, and low activity to seen towards c-Kit.
BPR1J-097 is a novel potent FLT3 inhibitor with an IC50 of 11 nM.
FLT3/D835Y-IN-1 (compound 13a) is a orally active, potent and selective FLT3 and FLT3/D835Y inhibitor, with IC50 values of 0.26 nM and 0.18 nM, respectively. FLT3/D835Y-IN-1 also blocks tumor growth, has anticancer efficacy, and can be used to research for AML (acute myeloid leukemia)[1].
FLT3-IN-3 is a potent FLT3 inhibitor with IC50s of 13 and 8 nM for FLT3 WT and FLT3 D835Y, respectively.
CG-806 is a pan FLT3/BTK Multi-Kinase inhibitor.
Dovitinib-D8 (CHIR-258-D8) is the deuterium labeled Dovitinib. Dovitinib (CHIR-258) is a multi-targeted tyrosine kinase inhibitor with IC50s of 1, 2, 8/9, 10/13/8, 27/210 nM for FLT3, c-Kit, FGFR1/FGFR3, VEGFR1/VEGFR2/VEGFR3 and PDGFRα/PDGFRβ, respectively[1][2].
Cabozantinib is a potent multiple receptor tyrosine kinases inhibitor that inhibits VEGFR2, c-Met, Kit, Axl and Flt3 with IC50s of 0.035, 1.3, 4.6, 7 and 11.3 nM, respectively.
Cabozantinib-d6 (XL184-d6) is the deuterium labeled Cabozantinib. Cabozantinib is a potent multiple receptor tyrosine kinases (RTKs) inhibitor that inhibits VEGFR2, c-Met, Kit, Axl and Flt3 with IC50s of 0.035, 1.3, 4.6, 7 and 11.3 nM, respectively[1][2][3].
Lestaurtinib (CEP-701;KT-5555) is a multi-kinase inhibitor with potent activity against the Trk family of receptor tyrosine kinases. Lestaurtinib inhibits JAK2, FLT3 and TrkA with IC50s of 0.9, 3 and less than 25 nM, respectively.
ENMD-2076 Tartrate is a multi-targeted kinase inhibitor with IC50s of 1.86, 14, 58.2, 15.9, 92.7, 70.8, 56.4 nM for Aurora A, Flt3, KDR/VEGFR2, Flt4/VEGFR3, FGFR1, FGFR2, Src, PDGFRα, respectively.
Tandutinib (MLN518, CT53518) is a potent FLT3 antagonist with IC50 of 0.22 μM, also inhibits PDGFR and c-Kit, 15 to 20-fold higher potency for FLT3 versus CSF-1R and >100-fold selectivity for the same target versus FGFR, EGFR and KDR. IC50 value: 0.22 uM [1]Target: Flt3; PDGFRβ; c-Kitin vitro: Tandutinib has little activity against EGFR, FGFR, KDR, InsR, Src, Abl, PKC, PKA and MAPKs. Tandutinib inhibits IL-3-independent cell growth and FLT3-ITD autophosphorylation with an IC50 of 10-100 nM. Tandutinib also inhibits the proliferation of human leukemia Ba/F3 cells containing FLT3-ITD mutations with IC50 values of 10-30 nM, and the FLT3-ITD-positive Molm-13 and Molm-14 cells with an IC50 of 10 nM. In FLT3-ITD-positive Molm-14 cells but not the FLT3-ITD-negative THP-1 cells, Tandutinib treatment leads to significant apoptosis by 51% and 78% at 24 and 96 hours, respectively, due to specific FLT3 inhibition [1]. Tandutinib preferentially inhibits the growth of blast colonies from FLT3 ITD-positive compared with ITD-negative patients with AML, without affecting colony formation by normal human progenitor cells [2].in vivo: Oral administration of Tandutinib at 60 mg/kg bid significantly increases the survival in mice bearing Ba/F3 cells expressing W51 FLT3-ITD mutant, and gives a significant reduction in mortality in a mouse bone marrow transplantation model [1]. Tandutinib treatment at 180 mg/kg twice daily has mild toxicity toward normal hematopoiesis, however, it is a dose at which Tandutinib is effective in treating FLT3 ITD-positive leukemia in mice [2].
Zeteletinib (BOS-172738) shows selective inhibitory activity against RET, PDGFR, KIT, NTRK and FLT3 kinases. Zeteletinib has antitumor activity[1].
MAX-40279 is a dual and potent inhibitor of FLT3 kinase and FGFR kinase. MAX-40279 has the potential for the research of acute myelogenous leukemia (AML) (extracted from patent WO2021180032)[1].
TCS 359, a 2-acylaminothiophene-3-carboxamide, is a potent inhibitor of FLT3 with IC50 of 42 nM. IC50 Value: 42 nM [1]Target: Flt3in vitro: TCS 359, a 2-acylaminothiophene-3-carboxamide, is a potent inhibitor of FLT3 with IC50 of 42 nM. TCS 359 inhibits MV4-11 proliferation with IC50 of 340 nM. TCS 359 is highly selective for FLT3 against a panel of kinases [1].
FLT3-IN-17 inhibits CYPs and FLT3 mutants activity (IC50s: <0.5 nM for D835Y). FLT3-IN-17 is also a FAK inhibitor, with an IC50 value of 12 nM. FLT3 ligand-2 can be used in the research of cancers[1].
FLT3-IN-16 is a potent FLT3 inhibitor with an IC50 of 1.1 μM. FLT3-IN-16 can be used for researching acute myeloid leukemia[1].
RSH-7 is a potent Btk and FLT3 inhibitor with IC50s of 47, 12 nM, respectively. RSH-7 induces apoptosis and shows antiproliferative activities. RSH-7 inhibits BTK and FLT3 signaling and shows anti-tumor activity[1].
TTT 3002 is a potent and orally active FLT3 inhibitor. TTT 3002 potently inhibits FLT3 phosphorylation by activating mutations at residue D835, with an IC50 of 0.2 nM. TTT 3002 can be used for AML (acute myeloid leukemia) research[1].
Linifanib (ABT-869) is a multi-targeted inhibitor of VEGF and PDGFR receptor family with IC50s of 3, 4, 66, 4 nM for KDR, Flt-1, PDGFRβ and FLT3, respectively.
SKLB4771 is a novel potent and selective Flt3 inhibitor with IC50 of 10 nM; against FLT3-ITD-expressing MV4-11 cells with IC50 of 6 nM.IC50 value: 10 nM (in vitro) [1]Target: in vitro: SKLB4771 inhibited FLT3 phosphorylation in a dose-dependent manner. Consistent with the downregulation of the phosphorylation of FLT3, the phosphorylation of the downstream signaling proteins STAT5 and ERK1/2 was also significantly inhibited at concentrations >0.1 μM. SKLB4771 potently inhibited the growth of MV4-11 cells that express FLT3-ITD, with an IC50 value of 0.006 μM. It just exhibited very weak inhibitory activity against human T lymphoma Jurkat cells, human Burkitt's lymphoma Ramos cells, human lung cancer PC-9 and H292 cells, and human epithelial carcinoma A431 cells (IC50: 3.05 μM, 6.25 μM, 3.72 μM, 6.94 μM, and 8.91 μM, respectively). For other leukemia and solid tumor cell lines, including K562, U937, Karpas299, HCC827, A549, H2228, H820, MDA-MB-231, BT474, MCF-7, HCT116, SW480, LoVo, HeLa, SKOV-3, SK, DU145, PC-3, A431, and SH-SY5Y [1].in vivo: Treatment with SKLB4771 at 100 mg/kg/d resulted in rapid and complete tumor regression in all mice of this group. SKLB4771 treatment at 20 mg/kg/d and 40 mg/kg/d significantly slowed down the tumor growth; the tumor inhibition rates are 66% and 84%, respectively. Moreover, during the whole experiment, no significant weight loss or any other obvious signs of toxicity were observed for all of the SKLB4771 treated mice.
AC710 is a potent PDGFR inhibitor with Kds of 0.6, 1.57, 1, 1.3, 1.0 nM for FLT3, CSF1R, KIT, PDGFRα and PDGFRβ, respectively.
Sorafenib (Bay 43-9006) is a potent multikinase inhibitor with IC50s of 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3, respectively.
PF 477736 is a potent, selective ATP-competitive inhibitor of Chk1, with a Ki of 0.49 nM, 100-fold selectivity versus Chk2 (Ki, 47 nM).
AKN-028 is an orally active and potent FLT3 tyrosine kinase inhibitor (IC50 = 6 nM). AKN-028 causes dose-dependent inhibition of FLT3 autophosphorylation[1].
HM43239 is an orally active and selective FLT3 inhibitor with IC50s 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 inhibits the kinase activity of FLT3 as a reversible type I inhibitor and modulates p-STAT5, p-ERK, SYK, JAK1/2, and TAK1. HM43239 inhibits the proliferation and induces the apoptosis of leukemic cells[1][2][3].
Sorafenib tosylate is a potent multikinase inhibitor, with IC50s of 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3, respectively.
FLT3/ITD-IN-2 (Compound 17) is a potent FLT3 internal tandem duplications (FLT3-ITD) inhibitor with IC50 values of 0.3, 0.4 and 1.0 nM against FLT3D835Y, FLT3 and FLT3-ITD, respectively. FLT3/ITD-IN-2 potently inhibits the phosphorylation of FLT3 and displays excellent antiproliferative activities against acute myeloid leukemia cell lines[1].