Merestinib (LY2801653) is a type-II ATP competitive, slow-off inhibitor of MET tyrosine kinase with a dissociation constant (Ki) of 2 nM.
MET kinase-IN-3 (compound 8) is an orally active and potent MET inhibitor, with an IC50 of 9.8 nM. MET kinase-IN-3 shows good and broad-spectrum antiproliferative activity against cancer cell lines[1].
Capmatinib (INCB28060) is a potent and selective c-MET kinase inhibitor. Capmatinib (INCB28060) inhibits c-MET kinase activity with an average IC50 of 0.13 nM.
MK-2461 is a novel ATP-competitive multitargeted inhibitor of activated c-Met with a mean IC50 of 2.5 nM.IC50 value: 2.5 nM [1]Target: c-Metin vitro: MK-2461 inhibits the kinase activity of human c-Met with a mean IC50 of 2.5 nM in the presence of 50 μM ATP. Ron (IC50 = 7 nM) and Flt1 (IC50 = 10 nM) are inhibited by MK-2461 with similar potencies to c-Met (IC50 = 2.5 nM), whereas nine other kinases, including FGFR1, FGFR2, FGFR3, PDGFRβ, KDR, Flt3, Flt4, TrkA, and TrkB, are found to be 8- to 30-fold less sensitive to MK-2461 than c-Met. [1]in vivo: MK-2461 inhibits c-Met signaling and tumor growth in tumor xenograft models in mice.[1]
Capmatinib (INC280; INCB28060) hydrochloride is a potent, orally active, selective, and ATP competitive c-Met kinase inhibitor (IC50=0.13 nM). Capmatinib hydrochloride can inhibit phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2, AKT, FAK, GAB1, and STAT3/5. Capmatinib hydrochloride potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis. Antitumor activity. Capmatinib hydrochloride is largely metabolized by CYP3A4 and aldehyde oxidase[1][2][3].
TAS-115 is a potent VEGFR and hepatocyte growth factor receptor (c-Met/HGFR)-targeted kinase inhibitor with IC50s of 30 and 32 nM for rVEGFR2 and rMET, respectively.
MK8033 is a novel and specific dual ATP competitive c-Met/Ron inhibitor (IC50=1 nM Wt c-Met) under investigation as a treatment for cancer.IC50 Value: 1 nM (Wt c-Met); 2.0 nM (c-Met N1100Y) [1]Target: c-Met/Ronin vitro: MK-8033 binds 3-fold more tightly to phosphorylated c-Met kinase domain (Kd= 3.2 nM) than to its unphosphorylated counterpart (Kd = 10.4 nM). Signigicantly, MK-8033 potently inhibits kinase activity of three oncogenic c-Met activation loop mutants, Y1230C, Y1230H, and Y1235D (IC50s ranging from 0.6 to 1 nM at 50 uM ATP) in addition to other c-Met activating mutants N1100Y and M1250T. MK-8033 potently inhibited GTL-16 proliferation with an IC50 of 582 ± 30 nM. By contrast the HCT116 cell line, which does not harbor basal c-Met activation, was not inhibited by MK-8033 (IC50 > 10000 nM) [1]. MK-8033 radiosensitized the high-c-Met-expressing EBC-1 and H1993 cells but not the low-c-Met-expressing cell lines A549 and H460. However, irradiation of A549 and H460 cells increased the expression of c-Met protein at 30 minutes after the irradiation. Subsequent targeting of this up-regulated c-Met by using MK-8033 followed by a second radiation dose reduced the clonogenic survival of both A549 and H460 cells. MK-8033reduced the levels of radiation-induced phosphorylated (activated) c-Met in A549 cells [2].in vivo: MK-8033 was orally dosed in GTL-16 tumor xenograft bearing mice. Mice were euthanized 1 h after dosing and tested for p-Met (Y1349) in tumors and MK-8033 concentrations in plasma. At 100 mg/kg,essentially complete inhibition of p-Met (Y1349) was achieved. An in vivo IC50 of 1.3 uM was deduced from the relationship between plasma MK-8033 level and Met pY1349. Treatment with escalating dosed of MK-8033 for 21 days lead to antitumor efficacies in a dose-dependent manner. Dosing at 3, 10, 30, and 100 mg/kg resulted in 22, 18, 57, and 86% tumor growth inhibition, respectively, relative to tumor from vehicle-treated mice.signatures.
BAY-474 is a tyrosine-protein kinase c-Met inhibitor. BAY-474 is a structural genomics consortium (SGC) epigenetics probe[1].
PF-04217903 phenolsulfonate is a potent ATP-competitive c-Met kinase inhibitor with Ki of 4.8 nM for human c-Met. PF-04217903 phenolsulfonate shows more than 1,000-fold selectivity relative to 208 kinases. Antiangiogenic properties[1][2].
PF-07265807 (PF 07265807) is a potent, selective dual Axl/Mer inhibitor, blocks Axl- and Mer-mediated signal transduction pathways, and inhibits proliferation and migration of Axl- and Mer-overexpressing tumor cells.
Emzeltrectinib is a potent tyrosine kinase inhibitor with antineoplastic activity[1][2].
c-Met/HDAC-IN-3 (Compound 15f) is a dual c-Met and HDAC inhibitor with IC50 values of 12.50 nM and 26.97 nM against c-Met and HDAC1, respectively. c-Met/HDAC-IN-3 induces apoptosis and cause cell cycle arrest in G2/M phase[1].
Crizotinib hydrochloride is a potent inhibitor of c-Met and ALK with IC50s of 11 nM and 24 nM in cell-based assays, respectively.
c-Met inhibitor 1 is an inhibitor of the c-Met receptor signaling pathway useful for the treatment of cancer including gastric, glioblastoma, and pancreatic cancer. IC50 value:Target: c-MetMore details please refer to Patent WO 2012015677 A1.
AMG-458 is a potent, selective and orally bioavailable c-Met inhibitor, with Ki values of 1.2 nM and 2.0 nM for human and mouse c-Met, respectively[1].
Resencatinib is a potent tyrosine kinase inhibitor with antineoplastic activity[1].
Ensartinib (X-396) is a potent and dual ALK/MET inhibitor with IC50s of <0.4 nM and 0.74 nM, respectively.
SU11274 is a selective Met inhibitor with IC50 of 10 nM, but has no effects on PGDFRβ, EGFR or Tie2.
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].
Multi-kinase-IN-1 (Compound 11k) is a potent kinase inhibitor with antitumor activity. Multi-kinase-IN-1 induces cell apoptosis, and can be studied for colorectal cancer[1].
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].
Glesatinib hydrochloride is an inhibitor of the MET and Axl receptor tyrosine kinase pathways, which drive tumour growth when altered.Target: MET, AxlGlesatinib is an orally bioavailable, small-molecule, multitargeted tyrosine kinase inhibitor with potential antineoplastic activity. MGCD265 binds to and inhibits the phosphorylation of several receptor tyrosine kinases (RTKs), including the c-Met receptor (hepatocyte growth factor receptor); the Tek/Tie-2 receptor; vascular endothelial growth factor receptor (VEGFR) types 1, 2, and 3; and the macrophage-stimulating 1 receptor (MST1R or RON). Glesatinib is a tyrosine kinase inhibitor that is expected to potently and selectively target tumors in patients with driver alterations in MET (mutations and gene amplification) and Axl (rearrangements) that occur in approximately 8% of patients with non-small cell lung cancer (NSCLC). Glesatinib is being evaluated in a Phase 1b study in patients with solid tumors that have genetic alterations in MET or AXL genes. The Phase 2 trial in NSCLC patients with MET genetic alterations is underway to confirm and extend the data that supports the clinical benefit of Glesatinib in patients with driver mutations in MET. Genetic alterations in these targets have been implicated as drivers of tumor growth and disease progression in NSCLC, gastroesophageal cancer and other solid tumors. MET and Axl are also implicated as drivers of tumor progression in patients whose tumors have become resistant to EGFR inhibitors. Therefore, Mirati believes that the combination of Glesatinib with an EGFR inhibitor could potentially treat patients who have become resistant to agents targeting EGFR. Mirati retains worldwide rights to Glesatinib.
Afatinib (BIBW 2992) oxalate is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC50 values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFRwt, EGFRL858R, EGFRL858R/T790M and HER2, respectively. Afatinib oxalate can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer[1][2][3][4].
EMD 1214063 is a potent and selective c-Met inhibitor with IC50 of 4 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer. IC50 Value: 4 nM [1]Target: c-Metin vitro: EMD 1214063 inhibits HGF-induced c-Met phosphorylation in A549 cells with IC50 of 6 nM. Treatment with EMD 1214063 induces a marked reduction of c-Met–constitutive phosphorylation in EBC-1 cells with IC50 of 9 nM. EMD 1214063 effectively blocka phosphorylation of the major downstream effectors of the c-Met enzyme, such as Grb2, Gab1, Sos, PLCγ, and phosphoinositide 3-kinase, in EBC-1, MKN-45, and Hs746T cells in the range of 1 to 10 nM. EMD 1214063 considerably inhibits the viability of MKN-45 cells with IC50 of less than 1 nM. Treatment with EMD 1214063 (as low as 0.1 nM) inhibits HGF-induced NCI-H441 cell migration, whereas concentrations of 100 nM to 1 μM almost completely prevents it.in vivo: EMD 1214063 treatment, at doses of 10 mg/kg or more, results in more than 90% inhibition of c-Met phosphorylation in Hs746T xenograft tumor for a period of at least 72 hours. EMD 1214063 induces more than 50% reduction of cyclin D1 expression, which persists after 96 hours upon treatment with doses of 100 mg/kg. A transient induction of p27 and cleaved caspase-3 are also observed upon treatment with EMD 1214063. EMD 1214063 (15 mg/kg, daily) treatment induces complete regression of gastric carcinoma xenografts Hs746T, in which c-Met is amplified, overexpressed, and activated in a ligand-independent fashion.
TAS-115 mesylate is a potent vascular endothelial growth factor (VEGFR) and hepatocyte growth factor receptor (c-Met/HGFR)-targeted kinase inhibitor, with IC50s of 30 and 32 nM for rVEGFR2 and rMET, respectively.
A Tyrosine kinase inhibitor.
Glumetinib (SCC244) is a potent and highly selective c-Met kinase inhibitor with an IC50 of 0.42 nM. Glumetinib shows antitumor activity and a superior safety margin[1].
Entacapone acid (Tyrphostin AG1290) is a tyrosine kinase inhibitor. Entacapone acid reduces hepatic protein synthesis rate (HPS) in vivo[1].
Tyrosine kinase-IN-6 is a potent and promising RON splice variants inhibitor with anti-cancer and o?antineoplastic effects[1].