Repositioning Candidate Details
| Candidate ID: | R1420 |
| Source ID: | DB11942 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Selinexor |
| Synonyms: | Selinexor |
| Molecular Formula: | C17H11F6N7O |
| SMILES: | FC(F)(F)C1=CC(=CC(=C1)C1=NN(\C=C/C(=O)NNC2=NC=CN=C2)C=N1)C(F)(F)F |
| Structure: |
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| DrugBank Description: | Selinexor is a first-in-class selective inhibitor of nuclear transport (SINE) compound. It is currently approved for the treatment of multiple myeloma, a cancer which forms from antibody-producing plasma cells. This condition is typically treated with high dose and dexamethasone chemotherapy followed by autologous stem-cell transplant. Other chemotherapies for multiple myeloma include and , , and may include if the patient is not eligible for transplant. Selinexor was approved by the FDA in June 2019. It was granted fast track and orphan designation as well as accelerated approval based on single arm, open label trial data. The Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma (BOSTON) trial is planned to finish in 2020. |
| CAS Number: | 1393477-72-9 |
| Molecular Weight: | 443.313 |
| DrugBank Indication: | Selinexor is indicated for the treatment of relapsed or refractory multiple myeloma in combination with dexamethasone. Patients must have received at least 4 prior therapies and have disease which is refractory to least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody. |
| DrugBank Pharmacology: | Selinexor causes cell cycle arrest and apoptosis in cancer cells. |
| DrugBank MoA: | Selinexor binds to and inhibits exportin-1 (XPO1). XPO1 is a nuclear exporter protein which contains a pocket to which nuclear proteins can bind. When complexed with these proteins and Ran, activated through guanosine triphosphate (GTP) binding, the XPO1-protein-Ran-GTP complex is able to exit the nucleus through a nuclear pore. Once outside, GTP is hydrolyzed and the complex dissociates. The inhibition of this process in cancer cells allows the targets of XPO1, many of which are tumor suppressors, to collect in the nucleus and result in increased transcription of tumor suppressor genes. Tumor suppressor proteins known to be affected by XPO1 inhibition include p53, p73, adenomatous polyposis coli, retinoblastoma, forkhead box protein O, breast cancer 1, nucleophosmin, and merlin. Regulators of cell cycle progression are also affected, namely p21, p27, galectin-3, and Tob. Inhibitor of NFκB also collects in the nucleus as a result leading to reduced activity of NFκB, a known contributor to cancer. XPO1 participates in the formation of a complex with eukaryotic initiation factor 4E and contributes to the transport of messenger RNA for several oncegenes including cell cycle promotors, cyclin D1, cyclin E, and CDK2/4/6, as well as antiapoptotic proteins, Mcl-1 and Bcl-xL. These wide ranging changes in protein expression and gene transcription culminate in cell cycle arrest and the promotion of apoptosis in cancer cells. |
| Targets: | Exportin-1 inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
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