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Ref Type Journal Article
PMID (28332364)
Authors Pei J, Chu T, Shao M, Teng J, Sha H, Gu A, Li R, Qian J, Mao W, Li Y, Han B
Title Potential Antitumor Activity of SIM-89 in Non-Small Cell Lung Cancer Cells.
Journal Vol Issue Date Pages Journal Short Title
Yonsei medical journal 58 3 2017 May 581-591 Yonsei Med J
URL
Abstract Text c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer.Z'-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases. Cell proliferation was then analyzed by CCK8 assay, and cell migration was determined by transwell assay. The gene expression and the phosphorylation of c-Met were examined by realtime-PCR and western blotting, respectively. Finally, the secretion of HGF was detected by ELISA assay.c-Met, activated protein kinase (AMPK), and tyrosine kinase A (TRKA) were inhibited by SIM-89 with the IC₅₀ values of 297 nmol/L, 1.31 μmol/L, and 150.2 nmol/L, respectively. SIM-89 exerted adenosine triphosphate (ATP) competitive inhibition on c-Met. Moreover, the expressions of STAT1, JAK1, and c-Met in H460 cells were decreased by SIM-89 treatment, and c-Met phosphorylation was suppressed in A549, H441, H1299, and B16F10 cells by the treatment. In addition, SIM-89 treatment significantly decreased the level of HGF, which accounted for the activation of c-Met receptor tyrosine kinase. Finally, we showed cell proliferation inhibition and cell migration suppression in H460 and H1299 cells after SIM-89 treatment.In conclusion, SIM-89 inhibits tumor cell proliferation, migration and HGF autocrine, suggesting it's potential antitumor activity.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
AZD2461 AZD2461 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
AZD2461 PARP Inhibitor (Pan) 30 AZD2461 inhibits PARP1 and PARP2, resulting in decreased tumor cell growth (PMID: 27550455, PMID: 28332364).
SIM-89 MET Inhibitor 59 TrkA Receptor Inhibitor 8 SIM-89 is an inhibitor of c-MET, TRKA, and AMPK, which may result in antitumor activity including inhibition of cell proliferation and suppression of cell migration (PMID: 28332364).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References