MELK-8a

Description: MELK-8a is a novel, highly potent and selective MELK (Maternal Embryonic Leucine Zipper Kinase) inhibitor. MELK kinase has been implicated in playing an important role in tumorigenesis. MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. MELK inhibitors 8a recapitulate the cellular effects observed by short hairpin ribonucleic acid (shRNA)-mediated MELK knockdown in cellular models. It was found that a novel fluorine-induced hydrophobic collapse that locked the ligand in its bioactive conformation and led to a 20-fold gain in potency. These novel pharmacological inhibitors achieved high exposure in vivo and were well tolerated, which may allow further in vivo evaluation.

Reference: J Med Chem. 2016 May 26; 59(10):4711-23.

Related CAS #: 2096992-20-8 (HCl)