WEE1 kinase has been reported to be aberrantly expressed in melanomas, glioblastoma multiforme (GBMs), triple negative breast cancers (TNBCs) and some prostate cancers. Dependence of various cancer cells on WEE1 signaling suggests that targeting epigenentic activity of WEE1 is a viable strategy for overcoming tumor proliferation.

Recently, we designed a novel assay that provides specific and quantitative measure of WEE1 epigenetic activity. Using this assay, we have screened the libraries and have identified two new scaffolds, both of which are highly efficient in suppressing WEE1 epigenetic activity. These two new class of WEE1 inhibitors not only suppress WEE1 kinase activity, but also have shown propensity to overcome WEE1 mediated cell cycle regulation. 

Feel free to contact us if you are interested in exploring these inhibitors in your system. 

Schematic outlining WEE1 epigenetic and non-epigenetic functions in cell cycle WEE1 is emerging as a critical surveyor of chromatin integrity across the evolutionary landscape by regulating histone synthesis and the cell cycle. It controls genome stability by regulating the activity of factors such as CDKs involved in replication initiation during S phase. During DNA replication, it negatively regulates the activity of the Mus81 endonuclease at stalled replication forks to prevent formation of DNA double strand breaks and preserve genetic integrity. Importantly, it appears to couple DNA synthesis with histone synthesis due to its ability to prevent mitotic entry until DNA synthesis is completed and to switch off histone transcription at the end of S phase. These functions are likely to be critical for its ability to delay chromosome condensation and prevent aneuploidy.

Translational Research