Selinexor

Selinexor is a first-in-class chemotherapeutic, functioning by binding to Exportin-1 (XPO1, CRM1), a nuclear membrane-associated protein that aids transport of proteins into the cytoplasm [1,2]. It also helps maintain chromosome structure [3]. Inhibition of these functions in cancer cells results in sensitization to DNA damaging agents, cell cycle arrest, and apoptosis [4,5]. For example, it suppresses growth of T-cell acute lymphoblastic leukemia (T-ALL) cells (IC50 = 34-203 nM) [6]. and pancreatic cancer cells (IC50 ~ 150 nM) [7]. Currently in clinical trials for COVID-19 because of its ability to reduce inflammation [8].

References:

1) A Degterev et al. Nat. Chem. Biol. 2005 1:112

2) X Dong et al. Nature 2009 458:1136

3) Y Adachi & M Yanagida J. Cell Biol. 1989 108:1195

4) T Kashyap et al. Oncotarget 2018 9:30773

5) HY Fung & YM Chook Semin. Cancer Biol. 2018 9:30773

6) J Etchin et al. Br. J. Haematol. 2013 161:117

7) AS Azmi et al. Gastroenterology 2013 144:447

8) J Taylor et al. Lancet Haematol. 2020 7: e566