Telatinib (Bay 57-9352) is an orally active, small molecule inhibitor of VEGFR2, VEGFR3, PDGFα, and c-Kit with IC50s of 6, 4, 15 and 1 nM, respectively.
Tafetinib (SIM010603) is an oral multi-targets receptor tyrosine kinases inhibitor. Tafetinib inhibitsstem cell factor receptor (Kit),vascular endothelial growth factor receptor-2 (VEGFR-2),platelet-derived growth factor receptor-β (PDGFR-β),glial cell line-derived neurotrophic factor receptor (Rearranged during Transfection; RET), andFms-like tyrosine kinase-3 (FLT3)withIC50values between 5.0 and 68.1 nmol/l. Tafetinib inhibits the phosphorylation ofPDGFR-βandVEGFR-2. Tafetinib inhibits endothelial cell proliferation, endothelial cells chemotaxis, and corneal angiogenesis[1].
AZD3229 Tosylate is a potent pan-KIT mutant inhibitor for the treatment of gastrointestinal stromal tumors.
Pexidartinib hydrochloride (PLX-3397 hydrochloride) is a potent, selective and ATP-competitive CSF1R (cFMS) and c-Kit inhibitor, with IC50s of 20 and 10 nM, respectively. Pexidartinib exhibits 10- to 100-fold selectivity for c-Kit and CSF1R over other related kinases, such as FLT3, KDR (VEGFR2), LCK, FLT1 (VEGFR1) and NTRK3 (TRKC), with IC50s of 160, 350, 860, 880, and 890 nM, respectively[1].
Apatinib free base (YN968D1 free base) is an orally bioavailable tyrosine kinase inhibitor, which selectively targets VEGFR-2 (IC50=1 nM). Apatinib free base (YN968D1 free base) is an anti-angiogenic drug for the treatment of advanced or metastatic gastric cancer. Apatinib free base (YN968D1 free base) potently inhibits Ret, c-Kit and c-Src with IC50s of 13, 429 and 530 nM, respectively. It also inhibits cellular phosphorylation of VEGFR-2, c-kit and PDGFRβ[1][2][3].
Regorafenib (BAY 73-4506) mesylate is an orally active and potent multi-targeted receptor tyrosine kinase inhibitor, with IC50 values of 13/4.2/46, 22, 7, 1.5 and 2.5 nM for VEGFR1/2/3, PDGFRβ, Kit, RET and Raf-1, respectively. Regorafenib mesylate shows very robust antitumor and antiangiogenic activity[1].
c-Kit-IN-2 is a c-KIT inhibitor with an IC50 of 82 nM, shows superior antiproliferative activities against all the three GIST cell lines, GIST882, GIST430, and GIST48, with GI50s of 3, 1, and 2 nM, respectively[1].
ISCK03 is a specific SCF/c-Kit inhibitor.
Masitinib mesylate is a novel inhibitor for Kit and PDGFRα/β with IC50 of 200 nM and 540 nM/800 nM, and has weak inhibition to ABL and c-Fms.
Labuxtinib is c-kit tyrosine kinase inhibitor[1].
Tyrphostin AG1296 is a potent and selective inhibitor of platelet-derived growth factor receptor (PDGFR), with an IC50 of 0.8 μM. Tyrphostin AG1296 inhibits signaling of human PDGF α- and β-receptors as well as of the related stem cell factor receptor (c-Kit). Tyrphostin AG1296 is also a potent inhibitor of FLT3, with an IC50 in the micromolar range[1][2][3].
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].
OSI-930 is a potent inhibitor of Kit, KDR and CSF-1R with IC50 of 80 nM, 9 nM and 15 nM, respectively; also potent to Flt-1, c-Raf and Lck and low activity against PDGFRα/β, Flt-3 and Abl.IC50 value: 9 nM(VEGFR2); 15 nM(CSF1R); 80 nM (Kit activated) [1]Target: VEGFR2/Kit/CSF1Rin vitro: OSI-930 inhibits the cell proliferation in the HMC-1 cell line with IC50 of 14 nM without significant effect on growth of the COLO-205 cell line that does not express a constitutively active mutant receptor tyrosine kinase. Moreover, OSI-930 also induces apoptosis in HMC-1 cell line with EC50 of 34 nM [1]. A recent study shows that OSI-930 inactivates purified, recombinant cytochrome P450 (P450) 3A4 with a Ki of 24 μM in a time- and concentration-dependent mode [2].in vivo: OSI-930, administrated at the maximally efficacious dose of 200 mg/kg by oral gavage, exhibits potent antitumor activity in a broad range of preclinical xenograft models including HMC-1, NCI-SNU-5, COLO-205 and U251 xenograft models [1].
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].
SU14813 is a multi-targeted receptor tyrosine kinases inhibitor with IC50s of 50, 2, 4, 15 nM for VEGFR2, VEGFR1, PDGFRβ and KIT.
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.
Pazopanib (GW786034) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ, c-Kit, FGFR1, and c-Fms with IC50s of 10, 30, 47, 84, 74, 140 and 146 nM, respectively.
SU14813 maleate is a multi-targeted receptor tyrosine kinases inhibitor with IC50s of 50, 2, 4, 15 nM for VEGFR2, VEGFR1, PDGFRβ and KIT.
Apatinib-d8 (free base) is the deuterium labeled Apatinib free base[1]. Apatinib free base (YN968D1 free base) is an orally bioavailable tyrosine kinase inhibitor, which selectively targets VEGFR-2 (IC50=1 nM). Apatinib free base (YN968D1 free base) is an anti-angiogenic drug for the treatment of advanced or metastatic gastric cancer. Apatinib free base (YN968D1 free base) potently inhibits Ret, c-Kit and c-Src with IC50s of 13, 429 and 530 nM, respectively. It also inhibits cellular phosphorylation of VEGFR-2, c-kit and PDGFRβ[2][3][4].
JI6 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 also inhibits JAK3 and c-Kit, with IC50s of ∼250 and ∼500 nM, respectively. JI6 can be used for the research of acute myeloid leukemia[1].
Bezuclastinib (CGT9486; PLX 9486) is a potent inhibitor of c-kit and c-kit D816V (0.0001
VEGFR-IN-1 (compound 3) is a potent angiogenesis inhibitor with IC50s of 0.02, 0.18, 0.24 7.3, and 7 µM for KDR, Flt-1, c-Kit, EGF-R, and c-Src, respectively[1].
Multi-kinase inhibitor 1 is a potent multi-kinase inhibitor. Multi-kinase inhibitor 1 has the potential for diseases or disorders associated with abnormal or deregulated tyrosine kinase activity, particularly diseases associated with the activity of PDGF-R, c-Kit and Bcr-abl[1].
Cabozantinib hydrochloride is a potent and orally active inhibitor of VEGFR2 and MET, with IC50 values of 0.035 and 1.3 nM, respectively. Cabozantinib hydrochloride displays strong inhibition of KIT, RET, AXL, TIE2, and FLT3 (IC50=4.6, 5.2, 7, 14.3, and 11.3 nM, respectively). Cabozantinib hydrochloride shows antiangiogenic activity. Cabozantinib hydrochloride disrupts tumor vasculature and promotes tumor and endothelial cell apoptosis[1].
Antitumor agent-70 (compound 8b) has anti-tumor activity and can induce cell apoptosis. Antitumor agent-70 inhibits multiple myeloma with an IC50 value of 0.12 μM. Antitumor agent-70 is a potential multi-targeted kinase inhibitor especially for c-Kit[1].
Imatinib is a tyrosine kinases inhibitor that inhibits c-Kit, Bcr-Abl, and PDGFR (IC50=100 nM) tyrosine kinases.
Imatinib Mesylate is a tyrosine kinases inhibitor that inhibits c-Kit, Bcr-Abl, and PDGFR (IC50=100 nM) tyrosine kinases.
AST 487 is a RET kinase inhibitor with IC50 of 880 nM, inhibits RET autophosphorylation and activation of downstream effectors, also inhibits Flt-3 with IC50 of 520 nM.
Toceranib-d8 (SU11654-d8) is the deuterium labeled Toceranib. Toceranib (SU11654) is an orally active receptor tyrosine kinase (RTK) inhibitor, and it potently inhibits PDGFR, VEGFR, and Kit with Kis of 5 and 6 nM for PDGFRβ and Flk-1/KDR, respectively. Toceranib (SU11654) has antitumor and antiangiogenic activity, and used in the treatment of canine mast cell tumors[1][2].
c-Met-IN-14 (compound 26af) is a selective inhibitor of c-Met kinase from N-sulfonylamidine-based derivatives, with an IC50 value of 2.89 nM. c-Met-IN-14 shows anticancer activity by blocking phosphorylation of c-Met, and arrests cell cycle at G2/M phase. c-Met-IN-14 induces apoptosis of A549 cells in a dose-dependent manner[1].