selinexor + pacritinib

Selinexor + pacritinib is an investigational combination therapy for myelofibrosis and other myeloproliferative neoplasms. **Selinexor** is a small molecule inhibitor of exportin 1 (XPO1), which induces apoptosis and inhibits proliferation through downregulation of nuclear export of tumor suppressor proteins and attenuation of the JAK/STAT pathway, as well as inhibition of NF-κB signaling. **Pacritinib** is a small molecule inhibitor of Janus kinase 2 (JAK2), FLT3, and IRAK1, selective for JAK2 over JAK1, which inhibits cell proliferation and survival signals in hematologic malignancies. The combination is being explored for its synergistic activity targeting both JAK-dependent and JAK-independent pathways including enhanced induction of cell cycle arrest and apoptosis. Both drugs are orally administered small molecules developed for the treatment of myelofibrosis and related neoplasms[1].