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Identification of KPNB1 as a Cellular Target of Aminothiazole Derivatives with Anticancer Activity
Author(s) -
Kim YongHak,
Ha Siyoung,
Kim Jungwon,
Ham Seung Wook
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600159
Subject(s) - chemistry , pharmacology , biology
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 ( K d : ∼20 n m ). 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.