The glycoglycerolipid 1,2-dipalmitoyl-3-(N-palmitoyl-6′-amino-6′-deoxy-α-d-glucosyl)-sn-glycerol is no inhibitor of the human Myt1 kinase

Abstract

Previously, a glycoglycerolipid isolated from marine algae was reported to be a potent and selective inhibitor of the human Myt1 kinase, an enzyme involved in cell cycle regulation with great potential as an anti-cancer target. Based on that report, a lot of research effort has been invested by several working groups to synthesize and derivatize this compound. However, reliable assay data confirming the inhibitory potential and the mechanism of action of these glycoglycerolipids are missing so far. Here, based on experimental data and theoretical considerations, we show that the aforesaid glycoglycerolipid 1,2-dipalmitoyl-3-(N-palmitoyl-6'-amino-6'-deoxy-α-d-glucosyl)-sn-glycerol is not an inhibitor of the human Myt1 kinase.

Genome-wide CRISPR-Cas9 Screens Reveal Loss of Redundancy between PKMYT1 and WEE1 in Glioblastoma Stem-like Cells

“…However, it is currently unclear whether PKMYT1 inhibition would synergize with cytotoxic therapies that engage WEE1 or whether this could suppress requirement for PKMYT1. Future studies will have to address this and also create pipelines for the identification of PKMYT1-specific inhibitors, which, to our knowledge, have not been successfully developed (Rohe et al, 2014a; Rohe et al, 2014b). …”

Fighting tubulin-targeting anticancer drug toxicity and resistance

“…So far, however, systematic development of specific MYT1 inhibitors has been hampered by lack of peptide substrates suitable for activity-based screening. Accordingly, GGL1, a glycoglycerolipid isolated from marine algae and reported to be a potent and selective inhibitor of the human MYT1 kinase, has failed to pass more specific functional assays (Göllner et al 2009, Rohe et al 2015a. The recent identification of MYT1 peptide substrates, using peptide microarrays, will hopefully allow the isolation of MYT1 inhibitors for testing in preclinical settings (Rohe et al 2015b).…”