NVP-BVU972 is a selective and potent Met inhibitor (IC50 = 14 nM). Antitumor agents.IC50 value: 14 nM [1]Target: MetNVP-BVU972 potently inhibits MET kinase but displays low inhibition against other kinases including the most closely related kinase RON with IC50 values of more than 1000 nM. NVP-BVU972 also suppresses constitutive MET phosphorylation in GTL-16 cells or HGF-stimulated MET phosphorylation in A549 cells with IC50 values of 7.3 nM and 22 nM, respectively. NVP-BVU972 potently prevents the growth of the MET gene amplified cell lines GTL-16, MKN-45 and EBC-1 with IC50 values of 66 nM, 82 nM and 32 nM, respectively. In line with their high frequency in the NVP-BVU972 screen, Y1230 and D1228 mutations give rise to dramatic shifts in the measured IC50 values for NVP-BVU972 in BaF3 cell line. Resistance triggered by V1155L is more limited to NVP-BVU972. A dose-dependent reduction in TPR-MET phosphorylation when applying NVP-BVU972 to BaF3 cells expressing wild-type TPR-MET. Both Y1230H and D1228A mutations abrogated the effect of NVP-BVU972 but not AMG 458. However, F1200I and L1195V interferes with the potency of NVP-BVU972 to prevent TPR-MET phosphorylation.
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].
Capmatinib (INC280; INCB28060) dihydrochloride is a potent, orally active, selective, and ATP competitive c-Met kinase inhibitor (IC50=0.13 nM). Capmatinib dihydrochloride 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 dihydrochloride potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis. Antitumor activity. Capmatinib dihydrochloride is largely metabolized by CYP3A4 and aldehyde oxidase[1][2][3].
c-Met/HDAC-IN-2 is a highly potent c-Met and HDAC dual inhibitor with IC50s of 18.49 nM and 5.40 nM for HDAC1 and c-Met, respectively. c-Met/HDAC-IN-2 has antiproliferative activities against certain cancer cell lines. c-Met/HDAC-IN-2 can cause G2/M-phase arrest and induce apoptosis in HCT-116. c-Met/HDAC-IN-2 can be used for researching anti-cancer resistance[1].
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].
c-Met-IN-15 (compound S3) is a c-Met kinase inhibitor. c-Met-IN-15 inhibits c-Met kinase activity of 21.1% at the concentration of 10 μM[1].
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.
Caveolin-1 (82-101) amide (human, mouse, rat) (Caveolin-1 scaffolding domain peptide) is a peptide that reverses aging-associated deleterious changes in multiple organs. Caveolin-1 (82-101) amide (human, mouse, rat) inhibits tyrosine kinases[1].
PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM, >50-fold selectivity for c-Met than RTKs or STKs.IC50 value: 9 nMTarget: c-Metin vitro: PHA-665752 significantly inhibits c-Met kinase activity with Ki of 4 nM, and exhibits >50-fold selectivity for c-Met compared with various tyrosine and serine-threonine kinases. PHA-665752 potently inhibits the HGF-stimulated c-Met autophosphorylation with IC50 of 25-50 nM. PHA-665752 also significantly blocks HGF- and c-Met-dependent functions such as cell motility and cell proliferation with IC50 of 40-50 nM and 18-42 nM, respectively. In addition, PHA-665752 potently inhibits HGF-stimulated or constitutive phosphorylation of mediators of downstream of c-Met such as Gab-1, ERK, Akt, STAT3, PLC-γ, and FAK in multiple tumor cell lines [1]. PHA-665752 inhibits cell growth in TPR-MET-transformed BaF3 cells with IC50 of <60 nM, and inhibits constitutive cell motility and migration by 92.5% at 0.2 μM. Inhibition of c-Met by PHA665752 (0.2 μM) also induces cell apoptosis of 33.1% and G1 cell cycle arrest with cells in G1 phase increasing from 42.4% to 77.0%. PHA665752 can cooperate with rapamycin to inhibit cell growth of TPR-MET-transformed BaF3 cells and non-small cell lung cancer H441 cells [2].in vivo: Administration of PHA-665752 induces a dose-dependent tumor growth inhibition of S114 xenografts by 20 %, 39% and 68%, at dose of 7.5, 15, and 30 mg/kg/day, respectively [1]. PHA665752 treatment significantly reduces the tumor growth of NCI-H69, NCI-H441 and A549 in mouse xenografts by 99%, 75%, and 59%, respectively. PHA665752 also significantly inhibits angiogenesis by >85%, due to decreasing the production of vascular endothelial growth factor and increasing the production of the angiogenesis inhibitor thrombospondin-1 [3].
Boditrectinib is a potent tyrosine kinase inhibitor. Boditrectinib serves as an antineoplastic agent. Boditrectinib is useful in the research of cancer, inflammation, neurodegenerative diseases and certain infectious diseases[1][2].
Ningetinib is a potent, orally bioavailable small molecule tyrosine kinase inhibitor (TKI) with IC50s of 6.7, 1.9 and <1.0 nM for c-Met, VEGFR2 and Axl, respectively.
Vabametkib is a potent inhibitor of hepatocyte growth factor receptor (HGFR). Vabametkib inhibits Hs746T cells proliferation and inhibits c-Met with an IC50 value of 7 nM. Vabametkib can be used as an antineoplastic agent[1][2].
MET kinase-IN-2 is a potent, selective, orally bioavailable MET kinase inhibitor with an IC50 of 7.4 nM. MET kinase-IN-2 has antitumor activity[1].
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.
Fosgonimeton is a hepatocyte growth factor receptor agonist (WO2017210489)[1].
c-Met-IN-2 is a potent, selective and orally available c-Met inhibitor, with an IC50 of 0.6 nM, with antitumor activity.
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].
c-Met-IN-13 is a potent c-Met inhibitor with an IC50 value of 2.43 nM. c-Met-IN-13 shows excellent cytotoxicity for cancer cells. c-Met-IN-13 shows antiproliferative activity in a concentration- and time- dependent manner. c-Met-IN-13 has the potential for the research of cancer[1].
BMS-794833 is a VEGFR2 and Met inhibitor extracted from patent WO2009094417, compound example 1; has IC50s of 15 and 1.7 nM, respectively.
Onartuzumab (MetMAb) is a unique, humanized and affinity-matured monovalent (one-armed) monoclonal antibody against the MET receptor. Onartuzumab potently inhibits HGF binding and receptor phosphorylation and signaling. Onartuzumab has antibody-like pharmacokinetics and antitumor activity[1].
Meleagrin is a roquefortine C-derived alkaloid produced by fungi of the genus Penicillium and has antimicrobial and anti-proliferative activities. Meleagrin is a class of FabI inhibitor. Meleagrin is a lead c-Met inhibitory entity useful for the control of c-Met-dependent metastatic and invasive breast malignancies[1][2][3].
Foretinib is a multi-target tyrosine kinase inhibitor with IC50s of 0.4 nM and 0.9 nM for Met and KDR.
Dalmelitinib is an orally active selective c-Met kinase inhibitor (IC50: 2.9 nM) that binds to the ATP-binding region of c-Met. Dalmelitinib induces the phosphorylation of MET, partially or completely inhibits the phosphorylation of AKT and ERK. Dalmelitinib potently inhibits cancer cell (c-Met oncogene amplification) proliferation, and is used for the research of cancers like human non-small cell lung cancer (NSCLC)[1].
Mifanertinib dimaleate is a potent tyrosine kinase inhibitor with antineoplastic activity[1].
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.
JNJ-38877605 is an ATP-competitive inhibitor of c-Met with IC50 of 4 nM, 600-fold selective for c-Met than 200 other tyrosine and serine-threonine kinases.IC50 value: 4 nM [1]Target: c-Metin vitro: JNJ-38877605 shows more than 600-fold selectivity for c-Met compared with more than 200 other diverse tyrosine and serine-threonine kinases and also potently inhibits HGF-stimulated and constitutively activated c-Met phosphorylation in vitro. [1] In EBC1, GTL16, NCI-H1993, and MKN45 cells, JNJ-38877605 (500 nM) leads to a significant reduction of phosphorylation of Met and RON, another key player in invasive growth [2]. A recent study shows that JNJ-38877605 is involved in modulating secretion of IL-8, GROa, uPAR and IL-6 in GTL16 cells [3]. in vivo: In mice bearing established GTL16 xenografts, JNJ-38877605, dosed orally with 40 mg/kg/day for 72 hours, results in a statistically significant decrease in the plasma levels of human IL-8 (from 0.150 ng/mL to 0.050 ng/mL) and GROα (from 0.080 ng/mL to 0.030 ng/mL). While concentrations of uPAR in the blood become reduced to more than 50% at the same dose [3].
SU 5616 is an organic compound. SU 5616 potentially modulates tyrosine kinase signal transduction, and regulates abnormal cell proliferation[1].
Altiratinib (DCC-2701) is a multi-targeted kinase inhibitor with IC50s of 2.7, 8, 9.2, 9.3, 0.85, 4.6, 0.83 nM for MET, TIE2, VEGFR2, FLT3, Trk1, Trk2, and Trk3 respectively.