exportin 1

Eltanexor (ONO-7706) is an orally active exportin-1 (XPO1) inhibitor. It has effective anti-leukemic activity. Eltanexor inhibits XPO1-dependent nuclear export (EC50=60.9 nM) by directly targeting XPO1. Eltanexor causes caspase-dependent apoptosis in a panel of leukemic cell lines.

Leptomycin B (LMB) is a potent inhibitor of the nuclear export of proteins and is a potent antifungal antibiotic blocking the eukaryotic cell cycle. Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue.

LFS-829 is a a small-molecule antagonist of exportin-1. LFS-829 showed low-range nanomolar activities. Oral administration of LFS-829 can significantly reverse the pathological features of colitis model mice. LFS-829 can attenuate dual NF-κB signaling and the Nrf2 cytoprotection pathway via targeting exportin-1 in colitis mice. Moreover, LFS-829 has a very low risk of cardiotoxicity and acute toxicity. LFS-829 holds great promise for the treatment of colitis and may warrant translation for use in clinical trials.

Leptomycin A, a metabolite derived from Streptomyces, acts as an inhibitor of CRM1 (exportin 1) and effectively suppresses HIV-1 replication. Compared to Leptomycin B, it exhibits lesser potency. Leptomycin A hampers the interaction between CRM1 and nuclear export signals, effectively hindering the nuclear export of a wide array of proteins.

KPT-251 is a selective nuclear export inhibitor.