177429-27-5Relevant articles and documents
Design, synthesis and biological evaluation of novel heptamethine cyanine dye-erlotinib conjugates as antitumor agents
Guo, Chun,Hou, Zhuang,Mou, Yanhua,Wang, Dun,Yang, Xiaoguang
supporting information, (2020/10/02)
Epidermal growth factor receptor tyrosine kinase (EGFR-TK) has been proved as a target for the treatment of non-small cell lung cancer (NSCLC) with specific gene mutations. However, EGFR-TK inhibitors (EGFR-TKIs) need to enter cancer cells and then competitively interact with the active site of tyrosine kinase receptors to suppress the downstream signaling pathway to inhibit tumor proliferation. In this study, in order to improve the tumor cell targeting ability of EGFR-TKI, EGFR-TKI erlotinib was conjugated with the cancer cell-targeting heptamethine cyanine dyes to form seventeen novel erlotinib-dye conjugates. The efficiency of tumor targeting properties of conjugates against cancer cell growth and EGFR-TK inhibition was evaluated in vitro. The result revealed that most erlotinib-dye conjugates exhibited stronger inhibitory effect on A549, H460, H1299 and MDA-MB-231 cell lines than the parent drug erlotinib. Meanwhile, representative compounds exhibited weak cytotoxicity on human normal mammary epithelial MCF-10A cells. Moreover, the conjugate CE17 also showed ~14-fold higher EGFR-TK inhibition activity (IC50 = 0.124 μM) than erlotinib (IC50 = 5.182 μM) in A549 cell line. Finally, molecular docking analysis verified that the erlotinib moiety of compound CE17 could form hydrogen bond with Met-769 and occupy active cavity of EGFR-TK. Therefore, we believed the integration strategy between heptamethine cyanine dyes and EGFR-TKI will contribute to enhancing the therapeutic effect of EGFR-TKI for NSCLC treatment.
Flavonoid metabolism: The synthesis of phenolic glucuronides and sulfates as candidate metabolites for bioactivity studies of dietary flavonoids
Zhang, Qingzhi,Raheem, K. Saki,Botting, Nigel P.,Slawin, Alexandra M.Z.,Kay, Colin D.,O'Hagan, David
, p. 4194 - 4201 (2012/07/14)
Epidemiological studies indicate that flavonoid intake is inversely associated with the risk of coronary heart disease, yet the mechanisms responsible for their bioactivity are still a matter of debate. Based on the rapid and extensive metabolism of most flavonoids, their health effects most likely result from the biological activity of their metabolites. However, a lack of commercially available compounds/standards has prevented the study of metabolite bioactivity and resulted in a focus on non-physiologically relevant precursor/parent structures. This paper details the synthesis of a series of phenolic glucuronide 1a-e and sulfate 2a-e derivates as candidate metabolites for use as reference compounds in metabolic profiling studies and for the exploration of flavonoid bioactivity.
VEGFR INHIBITORS CONTAINING A ZINC BINDING MOIETY
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Page/Page column 30, (2009/04/24)
The present invention relates to VEGFR inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The said derivatives may further act as HDAC inhibitors.
