Nuclear export receptor CRM1/XPO1 inhibitor. Blocks receptor XPO1, which interacts with SARS-CoV-2 replication machinery. Gordon et al. bioRxiv, Mar 23 2020, https://doi.org/10.1101/2020.03.22.002386; Laise et al. bioRxiv, May 17 2020, https://doi.org/10.1101/2020.05.12.091256.
Biochemicals & reagents
1) Etchin et al. (2013), KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-ALL and AML; Br. J. Haematol. 161 117 2) Azmi et al. (2013), Selective Inhibitors of Nuclear Export Block Pancreatic Cancer Cell Proliferation and Reduce Tumor Growth in Mice; Gastroenterology 144 447 3) Desisto et al. (2019), Exportin 1 inhibition induces nerve growth factor receptor expression to inhibit the NF-kB pathway in preclinical models of pediatric high-grade glioma; Mol. Cancer Ther. Epub ahead of print 4) Aboukameel et al. (2018), Down-regulation of AR splice variants through XPO1 suppression contributes to the inhibition of prostate cancer progression; Oncotarget 9 35327 5) Baek et al. (2018), XPO1 inhibition by selinexor induces potent cytotoxicity against high grade bladder malignancies; Oncotarget 9 34567 6) Wahba et al. (2018), The XPO1 Inhibitor Selinexor Inhibits Translation and Enhances the Radiosensitivity of Glioblastoma Cells Grown In Vitro and In Vivo; Mol. Cancer Ther. 17 1717 7) Arango et al. (2017), Selinexor (KPT-330) demonstrates anti-tumor efficacy in preclinical models of triple-negative breast cancer; Breast Cancer Res. 19 93 8) Conforti et al. (2017), Therapeutic Effects of XPO1 Inhibition in Thymic Epithelial Tumors; Cancer Res. 77 5614
Selinexor is a potent inhibitor of the nuclear export receptor, chromosome region maintenance 1 (CRM1; Exportin-1 (XPO1)) which has exhibited potent growth suppression in various T-cell acute lymphoblastic leukemia (T-ALL) cells with IC50’s = 34-203 nM (1) and in pancreatic cancer cells with IC50 ~ 150 nM (2). This compound is being investigated as a possible chemotherapeutic in treating multiple types of cancer (3-8) and is currently in clinical trials.