eEF-2K inhibitor 2C (Compound 2C) is a small molecule inhibitor of eukaryotic elongation factor 2 kinase (eEF-2K), binds to the ATP-binding site of eEF-2K.
eEF-2K inhibitor 2C (Compound 2C) (−7.691 kcal/mol) has better docking scores than some of the published eEF-2K inhibitors such as nonpotent inhibitor A484954 (−5.621 kcal/mol), NH125 (−4.503 kcal/mol), and TX-1918 (−5.533 kcal/mol), except for nonspecific eEF-2K inhibitor Rottlerin (−8.263 kcal/mol).
eEF-2K inhibitor 2C (Compound 2C) (<1 uM) inhibits proliferation and colony formation in breast cancer cells, including highly aggressive and invasive TNBC cells such as MDA-MB-231 (p53- and Kras-mutated), BT-20 (PI3K- and p53-mutated), and MDA-MB-436 (p53- and BRCA1-mutated) and noninvasive MCF-7 (ER+) cells.
eEF-2K inhibitor 2C (Compound 2C) inhibits activity of eEF-2K as indicated by reduced phosphorylation of its downstream target EF2, induces apoptosis in TNBC cells.
Treatment with single-lipid nanoparticle incorporating eEF-2K inhibitor 2C (Compound 2C) (20 mg/kg) significantly inhibited tumor growth, led to significant reduction in eEF-2K activity as indicated by reduced levels of p-EF2 (Thr56) in MDA-MB-231 tumor xenographs in highly aggressive TNBC tumor models.