c-Met-IN-2

c-Met-IN-2 is a selective and orally available c-Met inhibitor (IC50: 0.6 nM) exhibiting antitumor activity.

EGFR c-Met-IN-2 (Compound H-22) is a dual inhibitor of EGFR c-Met that arrests the G2 M phase to inhibit cell proliferation and demonstrates antitumor activity [1].

c-Met-IN-23 (Compound 12g) functions as a c-Met inhibitor with an IC50 of 0.052 μM against c-Met. It also inhibits the MDR1 and MRP1/2 pumps in cancerous HepG2 and BxPC3 cells. As such, c-Met-IN-23 serves as an anticancer agent.

c-Met/HDAC-IN-2 is a potent dual inhibitor of c-Met and HDAC, exhibiting IC50 values of 5.40 nM for c-Met and 18.49 nM for HDAC1, respectively. It demonstrates antiproliferative effects on various cancer cell lines, induces G2/M-phase arrest, and triggers apoptosis in HCT-116 cells, making it a promising candidate for anti-cancer resistance research.

VEGFR-2/c-Met-IN-1 is a dual inhibitor of VEGFR-2 and c-Met, with IC50 values of 138 nM and 74 nM, respectively, demonstrating antitumor activity [1].

c-Met-IN-26 (compound 1-170) is an effective inhibitor of c-Met, exhibiting an IC50 of 1.6 nM.

c-Met-IN-21 (compound 54) is a c-Met inhibitor with an IC50 value of 0.45 nM and exhibits antitumor activity in vivo.

c-Met-IN-22 (compound 51am) is an orally active c-Met inhibitor with an IC50 value of 2.54 nM. It exhibits both antiproliferative and antitumor activities and can induce apoptosis.

c-Met-IN-24 (compound 3g) serves as a dual-target inhibitor for STAT-3 (=4.7 μM) and c-MET (=12.67 μM), exhibiting anticancer properties. It arrests the G2 M cell cycle and induces apoptosis in SNB-75 cells, making it applicable in the research of central nervous system cancers.

JNK-IN-8 (JNK Inhibitor XVI) is an irreversible JNK1/2/4 inhibitor (IC50: 4.7/18.7/1 nM) with over 10-fold selectivity compared to MNK2 and Fms, and no inhibition of Met, c-Kit, or PDGFRβ in the A375 cell line.

T-1840383 is an inhibitor of VEGF-induced VEGFR-2 phosphorylation and HGF-induced c-Met phosphorylation in vascular endothelial cells and cancer epithelial cells.

CSF1R-IN-2 is an oral-active SRC, MET and c-FMS inhibitor (IC50s: 0.12 nM, 0.14 nM and 0.76 nM for SRC, MET and c-FMS respectively).

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.

Merestinib (LY2801653) is an orally available, small molecule inhibitor of the proto-oncogene c-Met (Ki: 2 nM) with potential antineoplastic activity. Merestinib electively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing the constitutively activated c-Met protein.

1. Herbacetin induces apoptosis in HepG2 cells, by ROS and PI3K/Akt pathway. 2. Herbacetin suppresses the HGF-induced motility of human breast cancer MDA-MB-231 cells by inhibiting c-Met and Akt phosphorylation.

c-Met-IN-11 is a potent inhibitor of c-MET (IC50: 41.4 nM) and VEGFR-2 (IC50: 71.1 nM).

Golvatinib (E-7050) is an orally bioavailable dual kinase inhibitor of c-Met (hepatocyte growth factor receptor) and VEGFR-2 (vascular endothelial growth factor receptor-2) tyrosine kinases with potential antineoplastic activity. c-Met/VEGFR kinase inhibitor E7050 binds to and inhibits the activities of both c-Met and VEGFR-2, which may inhibit tumor cell growth and survival of tumor cells that overexpress these receptor tyrosine kinases. c-Met and VEGFR-2 are upregulated in a variety of tumor cell types and play important roles in tumor cell growth, migration and angiogenesis.

Foretinib phosphate is an orally bioavailable small molecule with potential antineoplastic activity. MET VEGFR2 inhibitor GSK1363089 binds to and selectively inhibits hepatocyte growth factor (HGF) receptor c-MET and vascular endothelial growth factor receptor 2 (VEGFR2), which may result in the inhibition of tumor angiogenesis, tumor cell proliferation and metastasis. The proto-oncogene c-MET has been found to be over-expressed in a variety of cancers.

KRC-108 is a multiple kinase inhibitor. KRC-108 is a potent inhibitor of Ron, Flt3 and TrkA as well as c-Met. KRC-108 inhibited oncogenic c-Met M1250T and Y1230D more strongly than wild type c-Met. The anti-proliferative activity of KRC-108 was measured by performing a cytotoxicity assay on a panel of cancer cell lines. The GI(50) values (i.e., 50% inhibition of cell growth) for KRC-108 ranged from 0.01 to 4.22 μM for these cancer cell lines. KRC-108 was also effective for the inhibition of tumor growth in human HT29 colorectal cancer and NCI-H441 lung cancer xenograft models in athymic BALB c nu nu mice. This molecule should serve as a useful lead for inhibitors targeting kinases and may lead to new therapeutics for the treatment of cancer. (source: Invest New Drugs. 2012 Apr;30(2):518-23. doi: 10.1007 s10637-010-9584-2. Epub 2010 Nov 16. ).

MAPK-IN-2 (compound 3h) is an efficacious MAPK inhibitor with antineoplastic properties that significantly hinders proliferation across various cancer cell lines. It demonstrates robust suppression of the MAPK pathway (EGFR WT IC50 = 281 nM, c-MET IC50 = 205 nM, B-RAF WT IC50 = 112 nM, CDK4/6 IC50 = 95 and 184 nM, respectively) and exhibits pronounced activity against mutated forms of EGFR and B-RAF (EGFR T790M IC50 = 69 nM and B-RAF V600E IC50 = 83 nM) [1].