page_title: Selinexor
section_title: Mechanism of action
hierarchical_section_title: Selinexor / Mechanism of action
caption_attribution_description: Українська: RanГТФ - транспортний цикл
context_page_description: Selinexor is a selective inhibitor of nuclear export used as an anti-cancer drug. It works by binding to exportin 1 and thus blocking the transport of several proteins involved in cancer-cell growth from the cell nucleus to the cytoplasm, which ultimately arrests the cell cycle and leads to apoptosis. It is the first drug with this mechanism of action.
  The most common adverse reactions in people with diffuse large B-cell lymphoma, excluding laboratory abnormalities, were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia.
  Selinexor was granted accelerated approval by the U.S. Food and Drug Administration in July 2019, for use in combination with the corticosteroid dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma who have received at least four prior therapies and whose disease is resistant to several other forms of treatment, including at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. In clinical trials, it was associated with a high incidence of severe side effects, including low platelet counts and low blood sodium levels.
context_section_description: Like other selective inhibitors of nuclear export (SINEs), selinexor works by binding to exportin 1 (also known as XPO1 or  CRM1). XPO1 is a karyopherin which performs nuclear transport of several proteins, including tumor suppressors, oncogenes, and proteins involved in governing cell growth,  from the cell nucleus to the cytoplasm; it is often overexpressed and its function misregulated in several types of cancer. By inhibiting the XPO1 protein, SINEs lead to a buildup of tumor suppressors in the nucleus of malignant cells and reduce levels of oncogene products which drive cell proliferation. This ultimately leads to cell cycle arrest and death of cancer cells by apoptosis. In vitro, this effect appeared to spare normal (non-malignant) cells.
  Inhibiting XPO1 affects many different cells in the body which may explain the incidence of adverse reactions to selinexor. Thrombocytopenia, for example, is a mechanistic and dose-dependent effect, occurring because selinexor causes a buildup of the transcription factor STAT3 in the nucleus of hematopoietic stem cells, preventing their differentiation into mature megakaryocytes (platelet-producing cells) and thus slowing production of new platelets.
caption: Schematic illustration of the Ran cycle of nuclear transport. Selinexor inhibits this process at the nuclear export receptor (upper right).
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