496945-41-6Relevant academic research and scientific papers
Identification of KPNB1 as a Cellular Target of Aminothiazole Derivatives with Anticancer Activity
Kim, Yong-Hak,Ha, Siyoung,Kim, Jungwon,Ham, Seung Wook
supporting information, p. 1406 - 1409 (2016/07/16)
We found that aminothiazole derivative (E)-N-(5-benzylthiazol-2-yl)-3-(furan-2-yl)acrylamide (1) has strong anticancer activity, and undertook proteomics approaches to identify the target protein of compound 1, importin β1 (KPNB1). A competitive binding assay using fluorescein-labeled 1 showed that 1 has strong binding affinity for KPNB1 (Kd: ～20 nm). Furthermore, through western blotting assays for KPNB1, KPNA2, EGFR, ErbB2, and STAT3, we confirmed that 1 has inhibitory effects on the importin pathway. KPBN1 appears to be overexpressed in several cancer cells, and siRNA-induced inhibition of KPNB1 shows significant inhibition of cancer cell proliferation, while leaving non-cancerous cells unaffected. Therefore, compound 1 is a promising new lead for the development of KPNB1-targeted anticancer agents. Fluorescein-labeled 1 could be a useful quantitative probe for the development of novel KPNB1 inhibitors.
Synthesis and evaluation of 4-substituted benzylamine derivatives as β-tryptase inhibitors
Miyazaki, Yutaka,Kato, Yutaka,Manabe, Tadashi,Shimada, Hiroyasu,Mizuno, Masashi,Egusa, Takayuki,Ohkouchi, Munetaka,Shiromizu, Ikuya,Matsusue, Tomokazu,Yamamoto, Ichiro
, p. 2986 - 2990 (2008/09/20)
Since β-tryptase is considered a critical mediator of asthma, potent tryptase inhibitors may be useful as new agents for the treatment of asthma. We investigated 4-substituted benzylamine derivatives and obtained M58539 (15h) as a potent inhibitor of β-tryptase (IC50 = 5.0 nM) with high selectivity against other serine proteases, low molecular weight, c log P value less than 5, lack of amidino and guanidino groups, and independence of Zn2+ ion.
NOVEL AMINE DERIVATIVE HAVING HUMAN BETA-TRYPTASE INHIBITORY ACTIVITY AND DRUGS CONTAINING THE SAME
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Page 23, (2010/02/07)
It is intended to provide a novel low-molecular weight amine derivative, that is absorbed well, has low toxicity, and has an excellent human β-tryptase inhibitory activity with extremely high selectivity, a pharmaceutically acceptable salt thereof, and a medicine containing the same as an active ingredient. The medicine of the present invention is efficacious as a prophylactic/therapeutic agent for diseases in the crisis and evolution of which are considered to be attributed to β-tryptase, for example, respiratory diseases, allergic diseases, inflammatory bowel diseases, hyperprolliferative skin diseases, vascular edema and rheumatoid arthritis.
