github link
Accession IconGSE62477

MELK-T1, a small molecule inhibitor of protein kinase MELK, decreases DNA damage tolerance in highly proliferating cancer cells

Organism Icon Homo sapiens
Sample Icon 18 Downloadable Samples
Technology Badge Icon Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)

Submitter Supplied Information

Maternal Embryonic Leucine Zipper Kinase (MELK), a Ser/Thr protein kinase, is highly over expressed in stem and cancer cells. The oncogenic role of MELK is attributed to its capacity to disable critical cell cycle checkpoints and to enhance replication. Most functional studies have relied on the use of siRNA/shRNA-mediated gene silencing, but this is often compromised by off target effects. Here we present the cellular validation of a novel, potent and selective small molecule MELK inhibitor, MELK-T1, which has enabled us to explore the biological function of MELK. Strikingly, the binding of MELK-T1 to endogenous MELK triggers a rapid and proteasome dependent degradation of the MELK protein. Treatment of MCF-7 breast adenocarcinoma cells with MELK-T1 leads to an accumulation of stalled replication forks and double strand breaks, followed by a replicative senescence phenotype. This phenotype correlates with a rapid and long-lasting ATM activation and phosphorylation of CHK2. Furthermore, MELK-T1 induces strong phosphorylation of p53 and prolonged up-regulation of p21.
PubMed ID
Total Samples
Submitter’s Institution
Alternate Accession IDs


Show of 0 Total Samples
Accession Code
Cell line
Processing Information
Additional Metadata
No rows found