Inhibitors of nuclear transport

Central to eukaryotic cell function, transport into and out of the nucleus is largely mediated by members of the Importin (IMP) superfamily of transporters of α- and β-types. The first inhibitor of nuclear transport, leptomycin B (LMB), was shown to be a specific inhibitor of the IMPβ homologue Exportin 1 (EXP1) almost 20 years ago, but it has only been in the last five or so years that new inhibitors of nuclear export as well as import have been identified and characterised. Of utility in biological research, these inhibitors include those that target-specific EXPs/IMPs, with accompanying toxicity profiles, as well as agents that specifically target particular nuclear import cargoes. Both types of inhibitors have begun to be tested in preclinical/clinical studies, with particular focus on limiting various types of cancer or treating viral infection, and the most advanced agent targeting EXP1 (Selinexor) has progressed successfully through >40 clinical trials for a range of high-grade cancers and is approaching FDA approval for a number of indications. Selectively inhibiting the nucleocytoplasmic trafficking of specific proteins of interest remains a challenge, but progress in the area of the host–pathogen interface holds promise for the future.