GB2643430A — Nuclear transport inhibitors for anti-cancer combination therapy

USPTO Abstract

A combination for use in treating cancer comprising: (a) a compound of Formula I or a pharmaceutically acceptable salt thereof, and (b) a compound of Formula II or pharmaceutically acceptable salt thereof is provided: wherein R1 is a branched or linear C2-C5 alkyl group optionally functionalised with an amine, imidazole, alcohol or morpholine; R2 is selected from hydrogen or methyl; X1 is a hydrogen or methyl group; X2 is a cyclic group as defined herein, or X1 and X2 together with the N atom form a heterocyclic group as defined herein; X3 is a hydrogen or halogen; and the olefin bond may be either in the (E)- or (Z)-configuration. The cancer may be cervical cancer, oesophageal cancer, ovarian cancer, uterine cancer, breast cancer or multiple myeloma. The compound of Formula I is an inhibitor of the nuclear import transport receptor Karyopherin Beta 1 (Kpnβ1, Importin β) such as INI-43. The compound of Formula II is an inhibitor of the nuclear export transport receptor Chromosome Maintenance 1 (Crm1, Exportin 1, XPO1) such as Selinexor (XPOVIO, KPT-330).