Eltanexor

Eltanexor is an inhibitor of exportin 1 (XPO1/CRM1).¹ It inhibits the binding of XPO1/CRM1 to various nuclear export signals (NESs) in cell-free pull-down assays when used at a concentration of 10 µM. Eltanexor inhibits Cas9-encoding mRNA nuclear export in HEK293T cells in a concentration-dependent manner and CRISPR-Cas9 gene editing in a reporter assay using HEK293 cells (IC₅₀ = 94 nM).² It inhibits human cytomegalovirus (CMV) replication in primary human foreskin fibroblasts (IC₅₀ = 37.62 nM).³ Eltanexor (100 nM) induces IκBα and NF-κB p65 nuclear accumulation and inhibits RANKL-induced osteoclast differentiation in isolated mouse bone marrow-derived macrophages (BMDMs).⁴ It induces apoptosis in primary human chronic lymphocytic leukemia (CLL) cells and increases survival and decreases spleen leukemic burden in an MV4-11 acute myeloid leukemia (AML) mouse xenograft model.¹ Eltanexor (5 mg/kg five times per week) also increases locomotor activity and tibialis anterior myofiber size and decreases serum osteopontin (OPN) levels in the D2-mdx mouse model of Duchenne muscular dystrophy (DMD).⁵

WARNING This product is not for human or veterinary use.

1. Hing, Z.A., Fung, H.Y., Ranganathan, P., et al. Next-generation XPO1 inhibitor shows improved efficacy and in vivo tolerability in hematological malignancies. Leukemia 30(12), 2364-2372 (2016).

2. Cui, Y.R., Wang, S.J., Ma, T., et al. KPT330 improves Cas9 precision genome- and base-editing by selectively regulating mRNA nuclear export. Commun. Biol. 5(1), 237 (2022).

3. Liao, Y., Ke, X., Deng, T., et al. The second-generation XPO1 inhibitor eltanexor inhibits human cytomegalovirus (HCMV) replication and promotes type I interferon response. Front. Microbiol. 12:675112, (2021).

4. Chen, J., Song, D., Xu, Y., et al. Anti-osteoclast effect of exportin-1 inhibitor eltanexor on osteoporosis depends on nuclear accumulation of IκBα-NF-κB p65 complex. Front. Pharmacol. 13:896108, (2022).

5. English, K.G., Reid, A.L., Samani, A., et al. Next-generation SINE compound KPT-8602 ameliorates dystrophic pathology in zebrafish and mouse models of DMD. Biomedicines 10(10), 2400 (2022).