Abstract 1742: Inhibition of Mer tyrosine kinase with a novel small molecule inhibitor is efficacious in pre-clinical models of non-small cell lung cancer

2014 ◽  
Author(s):  
Christopher T. Cummings ◽  
Kurtis D. Davies ◽  
Jacqueline Carrico ◽  
Deborah DeRyckere ◽  
Weihe Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Molecule Inhibitor ◽  
Clinical Models ◽  
Mer Tyrosine Kinase

scholarly journals Dramatic Antitumor Effects of the Dual MET/RON Small-Molecule Inhibitor LY2801653 in Non–Small Cell Lung Cancer

2013 ◽  
Vol 74 (3) ◽  
pp. 884-895 ◽  
Author(s):  
Ichiro Kawada ◽  
Rifat Hasina ◽  
Qudsia Arif ◽  
Jeffrey Mueller ◽  
Erin Smithberger ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Molecule Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Antitumor Effects ◽  
Molecule Inhibitor

A Novel Small-Molecule Inhibitor of Protein Kinase Cι Blocks Transformed Growth of Non–Small-Cell Lung Cancer Cells

2006 ◽  
Vol 66 (3) ◽  
pp. 1767-1774 ◽  
Author(s):  
Melody Stallings-Mann ◽  
Lee Jamieson ◽  
Roderick P. Regala ◽  
Capella Weems ◽  
Nicole R. Murray ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protein Kinase ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Molecule Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Molecule Inhibitor

scholarly journals Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Kaili Long ◽  
Lili Gu ◽  
Lulu Li ◽  
Ziyu Zhang ◽  
Enjie Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Molecular Compound ◽  
Small Cell Lung

AbstractApurinic/apyrimidinic endonuclease 1 (APE1) plays a critical role in the base excision repair (BER) pathway, which is responsible for the excision of apurinic sites (AP sites). In non-small cell lung cancer (NSCLC), APE1 is highly expressed and associated with poor patient prognosis. The suppression of APE1 could lead to the accumulation of unrepaired DNA damage in cells. Therefore, APE1 is viewed as an important marker of malignant tumors and could serve as a potent target for the development of antitumor drugs. In this study, we performed a high-throughput virtual screening of a small-molecule library using the three-dimensional structure of APE1 protein. Using the AP site cleavage assay and a cell survival assay, we identified a small molecular compound, NO.0449-0145, to act as an APE1 inhibitor. Treatment with NO.0449-0145 induced DNA damage, apoptosis, pyroptosis, and necroptosis in the NSCLC cell lines A549 and NCI-H460. This inhibitor was also able to impede cancer progression in an NCI-H460 mouse model. Moreover, NO.0449-0145 overcame both cisplatin- and erlotinib-resistance in NSCLC cell lines. These findings underscore the importance of APE1 as a therapeutic target in NSCLC and offer a paradigm for the development of small-molecule drugs that target key DNA repair proteins for the treatment of NSCLC and other cancers.

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