targetsTarget

Exportin-1 (XPO1)

The export pump that carries tumour suppressor proteins such as p53 out of the nucleus, where they cannot act. Selinexor blocks it so those brakes stay in the nucleus and cancer cells die.

Exportin-1, also called CRM1, shuttles more than 200 cargo proteins from the nucleus to the cytoplasm, including p53, p21, FOXO, IkB and the eIF4E-bound oncogene messenger RNAs. Many cancers overexpress it, keeping tumour suppressors out of the nucleus. Selinexor binds covalently to cysteine 528 of XPO1, trapping the suppressors inside the nucleus; it is approved for relapsed multiple myeloma and diffuse large B-cell lymphoma, and is under study in TP53 wild-type endometrial cancer. Nausea, anorexia, weight loss and thrombocytopenia are its main side effects.

Exportin-1 (XPO1): what it is and how drugs act on it · animated generic schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · The export pump that carries tumour suppressor proteins such as p53 out of the nucleus, where they cannot act. Selinexor blocks it so those brakes stay in the nucleus and cancer cells die.

1 · What it is
The export pump that carries tumour suppressor proteins such as p53 out of the nucleus, where they cannot act. Selinexor blocks it so those brakes stay in the nucleus and cancer cells die.
2 · What goes wrong in cancer
Karyopherin that exports nuclear export signal-bearing proteins and some RNAs; inhibited covalently by selinexor at Cys528.
3 · How drugs use it
No product in this corpus aims at Exportin-1 (XPO1) yet. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.