The mechanism of action of KPT-SINE. The top half represents a typical AML cell, in which tumor suppressor (TS) proteins (small orange circles) escape through the nuclear membrane via the CRM1 nuclear exporter, resulting in a distribution of TS proteins throughout the cell. Arrows indicate the outward direction of flow of the TS proteins from the nucleus into the cytoplasm. In the bottom half, KPT-SINE irreversibly locks the transporter into a conformation that blocks the normal efflux of TS proteins from the nucleus, facilitating their accumulation within the nucleus and potentially allowing TS function. Professional illustration by Alice Y. Chen.