Eltanexor

Eltanexor is an inhibitor of exportin 1 (XPO1/CRM1). 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). It inhibits human cytomegalovirus (CMV) replication in primary human foreskin fibroblasts (IC50 = 37. nM). Eltanexor (100 nM) induces IkappaBalpha and NF-kappaB p65 nuclear accumulation and inhibits RANKL-induced osteoclast differentiation in isolated mouse bone marrow-derived macrophages (BMDMs). 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. 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). InChI: InChI=1S/C17H10F6N6O/c18-16(19,20)11-1-9(2-12(3-11)17(21,22)23)15-27-8-29(28-15)6-13(14(24)30)10-4-25-7-26-5-10/h1-8H,(H2,24,30)/b13-6+ InChIKey: JFBAVWVBLRIWHM-AWNIVKPZSA-N SMILES: O=C(/C(C1=CN=CN=C1)=C/N2C=NC(C3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)=N2)N