About XPOVIO®

XPOVIO® is the FIRST and ONLY XPO1 inhibitor for multiple myeloma, helping to restore tumor suppressor pathways in the cell's nucleus, leading to cell cycle arrest and apoptosis.

Cancer cell not explosed to XPOVIO®
  • XPO1 is overexpressed.1-3
  • The nuclear export of the cargos, including tumor suppressor proteins, into the cytoplasm is increased.1,3-6
  • With these important cargos mislocalized, the cancer cell is free to grow and survive.2-4
Cancer cell explosed to XPOVIO®
  • In non-clinical settings, selinexor reversibly inhibits nuclear export of TSPs, growth regulators, and mRNAs of growth promoting (oncogenic) proteins by specifically blocking XPO1.
  • XPO1 inhibition by selinexor leads to marked accumulation of TSPs in the nucleus, cell cycle arrest, reductions in several oncoproteins such as c-Myc and cyclin D1, and apoptosis of cancer cells.
  • XPO1 is overexpressed.1-3
  • The nuclear export of the cargos, including tumor suppressor proteins, into the cytoplasm is increased.1,3-6
  • With these important cargos mislocalized, the cancer cell is free to grow and survive.2-4
  • In non-clinical settings, selinexor reversibly inhibits nuclear export of TSPs, growth regulators, and mRNAs of growth promoting (oncogenic) proteins by specifically blocking XPO1.
  • XPO1 inhibition by selinexor leads to marked accumulation of TSPs in the nucleus, cell cycle arrest, reductions in several oncoproteins such as c-Myc and cyclin D1, and apoptosis of cancer cells.
  • The combination of selinexor and dexamethasone was evaluated in patients with disease refractory/resistant to dexamethasone and proteasome inhibitors and in cell lines, both of which demonstrated activity and synergy for the combination including when proteasome inhibition was present.
  • The combination of selinexor and bortezomib was evaluated in cells and murine xenograft multiple myeloma models in vivo, including cells and models resistant to proteasome inhibitors.

TSPs, tumor suppressor proteins; XPO1, exportin 1.

References
1. Yang J, Bill MA, Young GS, et al. Novel small molecule XPO1/CRM1 inhibitors induce nuclear accumulation of TP53, phosphorylated MAPK and apoptosis in human melanoma cells. PLoS One. 2014;9(7):e102983.
2. Gupta A, Saltarski JM, White MA, Scaglioni PP, Gerber DE. Therapeutic targeting of nuclear export inhibition in lung cancer. J Thorac Oncol. 2017;12(9):1446-1450.
3. Mor A, White MA, Fontoura BM. Nuclear trafficking in health and disease. Curr Opin Cell Biol. 2014;28:28-35.
4. Sun Q, Chen X, Zhou Q, Burstein E, Yang S, Jia D. Inhibiting cancer cell hallmark features through nuclear export inhibition. Signal Transduct Target Ther. 2016;1:16010.
5. Gravina GL, Senapedis W, McCauley D, Baloglu E, Shacham S, Festuccia C. Nucleo-cytoplasmic transport as a therapeutic target of cancer. J Hematol Oncol. 2014;7:85.
6. Tai YT, Landesman Y, Acharya C, et al. CRM1 inhibition induces tumor cell cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular mechanisms and therapeutic implications. Leukemia. 2014;28(1):155-165.