Selinexor (Xpovio)

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Mechanism of action

From NCI Drug Dictionary: An orally available, small molecule inhibitor of CRM1 (chromosome region maintenance 1 protein, exportin 1 or XPO1), with potential antineoplastic activity. Selinexor modifies the essential CRM1-cargo binding residue cysteine-528, thereby irreversibly inactivating CRM1-mediated nuclear export of cargo proteins such as tumor suppressor proteins (TSPs), including p53, p21, BRCA1/2, pRB, FOXO, and other growth regulatory proteins. As a result, this agent, via the approach of selective inhibition of nuclear export (SINE), restores endogenous tumor suppressing processes to selectively eliminate tumor cells while sparing normal cells.

Diseases for which it is used

History of changes in FDA indication

Diffuse large B-cell lymphoma

Multiple myeloma

  • 7/3/2019: Granted accelerated approval in combination with dexamethasone for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. (Based on STORM)
  • 12/18/2020: Approved in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. (Based on BOSTON)

Also known as

  • Code name: KPT-330
  • Brand name: Xpovio