Importazole, a small molecule inhibitor of the transport receptor importin-β, can be used to assess the function of the importin-β/RanGTP pathway at specific stages of the cell cycle[1].
In vitro, Importazole (10μM; 24h) treatment reduced the nuclear localization of IRF1 in Ca9-22 cells[2]. Blocking p85β nuclear translocation by Importazole enhances Alpelisib efficacy against PIK3CA-helical-domain-mutant tumors[3]. Inhibition of the nuclear transport protein Importin-β with Importazole (40µM; 4h) in MAC-T cells reduces ribotoxin-induced nuclear localization of IGFBP-3[4].
In vivo, Combination of Importazole (6.25mg/kg; 3 weeks; i.p.) and Alpelisib (p110α-specific inhibitor) significantly inhibited the growth of DLD1 cells, DLD1 xenograft tumors, and two patient-derived xenograft tumors harboring a PIK3CA E545K mutation[3]. Pharmacological inhibition of KPNB1 using the specific inhibitor Importazole (20mg/kg/3 times a week; 2 weeks; i.p.) significantly reduced tumor burden and prolonged survival in MLL-AF9-induced Acute myeloid leukemia (AML) mice[5].
References:
[1] Soderholm JF, Bird SL, Kalab P, et al. Importazole, a small molecule inhibitor of the transport receptor importin-β. ACS Chem Biol. 2011 Jul 15;6(7):700-8.
[2] Yoshino H, Sato Y, Nakano M. KPNB1 Inhibitor Importazole Reduces Ionizing Radiation-Increased Cell Surface PD-L1 Expression by Modulating Expression and Nuclear Import of IRF1. Curr Issues Mol Biol. 2021 May 19;43(1):153-162.
[3] He B, Li X, Yao M, et al. Blocking p85β nuclear translocation by importazole enhances Alpelisib efficacy against PIK3CA-helical-domain-mutant tumors. Biochem Biophys Res Commun. 2025 Feb 8;748:151324.
[4] Agostini-Dreyer A, Jetzt AE, Skorupa J, et al. IGFBP-3 Induced by Ribotoxic Stress Traffics From the Endoplasmic Reticulum to the Nucleus in Mammary Epithelial Cells. J Endocr Soc. 2018 Dec 24;3(3):517-536.
[5] Xie Y, Zhao R, Zheng Y, et al. Targeting KPNB1 suppresses AML cells by inhibiting HMGB2 nuclear import. Oncogene. 2025 Jun;44(21):1646-1661. doi: 10.1038/s41388-025-03340-0. Epub 2025 Mar 13.
Importazole是一种小分子抑制剂，能够抑制转运受体Importin-β的功能，可用于评估细胞周期特定阶段Importin-β/RanGTP通路的功能[1]。
体外实验中，Importazole（10μM; 24小时）处理降低了Ca9-22细胞中IRF1的核定位[2]。通过Importazole阻断p85β的核转位可以增强Alpelisib（PIK3CA螺旋结构域突变肿瘤的抑制剂）的疗效[3]。在MAC-T细胞中，使用Importazole（40µM; 4小时）抑制核转运蛋白Importin-β可以减少核糖体毒素诱导的IGFBP-3的核定位[4]。
体内实验中，Importazole（6.25mg/kg; 3周; 腹腔注射）与Alpelisib（p110α特异性抑制剂）的联合使用显著抑制了DLD1细胞、DLD1异种移植瘤以及携带PIK3CA E545K突变的两种患者来源异种移植瘤的生长[3]。使用特异性抑制剂Importazole对KPNB1进行药理学抑制，显著减少了MLL-AF9诱导的急性髓系白血病（AML）小鼠模型中的肿瘤负荷，并延长了小鼠的生存期[5]。