ARN-0953 is an orally available, selective and brain penetrable small molecule inhibitor of Maternal Embryonic Leucine zipper Kinase (MELK) currently in IND enabling stage of development for the future treatment of AML and other cancers.
MELK is a snf1/AMPK family member of Ser/Thr kinase and has a unique amino acid sequence in the catalytic loop of the kinase domain and is a key regulator of in cell cycle, self-renewal of stem cells, apoptosis, mammary and glial stem cells. MELK has broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622 and it phosphorylates and activates MAP3K5/ASK1.
MELK found to be over-expressed in multiple cancers particularly in AML, TNBC subtype basal-like breast cancer, brain tumors (glioblastoma multiforme or astrocytoma), melanoma and lung cancers.
A selective inhibition of MELK activity could be a promising therapeutic strategy for treating AML, breast and GBM cancers types. ARN-0953 is potent, high ligand efficient MELK inhibitor to target specifically AML cancers and was discovered using company proprietary platform.