Investigating the specificity of the small molecule inhibitor INI-43 for Kpn?1 in cancer cells

Karyopherin beta1 (Kpnbeta1) is the major nuclear import protein involved in the shuttling of cargo proteins and mRNAs into the cell nucleus. Recent studies have found that Kpnbeta1 levels are significantly upregulated in cancer cells, and that targeted inhibition of Kpn?1 with siRNA results in reduced proliferation and the induction of apoptosis, suggesting that Kpnbeta1 is important for cancer cell survival. Inhibitor of Nuclear Import-43 (INI-43) is a small molecule inhibitor identified in our laboratory as having the potential to interfere with the nuclear import function of Kpn?1. It has been shown to inhibit the nuclear localization of both Kpn?1 and known Kpnbeta1 cargoes such as NF?B and NFAT, as well as inhibit the proliferation of cancer cells of different tissue origins. This study aimed to investigate the specificity of INI-43 for Kpnbeta1 by performing experiments to determine whether expression of exogenous Kpnbeta1-GFP was able to rescue cells from the effects of INI-43 treatment. The results suggest that the small molecule inhibitor INI-43 is acting, at least in part, by targeting Kpn?1.