4655-54-3Relevant academic research and scientific papers
Suppression of Drug-Resistant Non-Small-Cell Lung Cancer with Inhibitors Targeting Minichromosomal Maintenance Protein
Lin, Chia-Yi,Wu, Hsin-Yi,Hsu, Yuan-Ling,Cheng, Ting-Jen Rachel,Liu, Jyung-Hurng,Huang, Rou-Jie,Hsiao, Tzu-Hung,Wang, Chia-Jen,Hung, Pei-Fang,Lan, Albert,Pan, Szu-Hua,Chein, Rong-Jie,Wong, Chi-Huey,Yang, Pan-Chyr
, p. 3172 - 3187 (2020)
Drug resistance has been a major threat in cancer therapies that necessitates the development of new strategies to overcome this problem. We report here a cell-based high-throughput screen of a library containing two-million molecules for the compounds that inhibit the proliferation of non-small-cell lung cancer (NSCLC). Through the process of phenotypic screening, target deconvolution, and structure-activity relationship (SAR) analysis, a compound of furanonaphthoquinone-based small molecule, AS4583, was identified that exhibited potent activity in tyrosine kinase inhibitor (TKI)-sensitive and TKI-resistant NSCLC cells (IC50 = 77 nM) and in xenograft mice. The mechanistic studies revealed that AS4583 inhibited cell-cycle progression and reduced DNA replication by disrupting the formation of the minichromosomal maintenance protein (MCM) complex. Subsequent SAR study of AS4583 gave compound RJ-LC-07-48 which exhibited greater potency in drug-resistant NSCLC cells (IC50 = 17 nM) and in mice with H1975 xenograft tumor.
4,9-DIOXO-4,9-DIHYDRONAPHTHO(2,3-B)FURAN-3-CARBOXMIDE DERIVATIVES AND USES THEREOF FOR TREATING PROLIFERATIVE DISEASES AND INFECTIOUS DISEASES
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, (2017/09/15)
The present disclosure provides compounds of Formulas (I), (II), and pharmaceutically acceptable salts thereof. The compounds described herein are useful in treating proliferative diseases, for example, cancer (e.g., lung cancer), and infectious diseases (e.g., bacterial infections).
