Mercachem logo voor websites

Update COVID-19:

The COVID-19 situation is currently impacting most of the globe, including Asia, Europe and North America. At all MercachemSyncom sites, we follow the recommendations of the local competent authorities as they are released. We have established a series of contingency measures aimed at reducing risks for our employees, their families and the MercachemSyncom Operations. These measures are proactively being reassessed at regular intervals and adapted as deemed appropriate.

The MercachemSyncom team is united and determined to face the situation with the energy, strength and passion that constitute one of our hallmarks.

Article RULE


Innovation is always an important focus for Mercachem. Together with our partner ProQinase, we embarked on a mission to turn literature-reported histone lysine methyltransferase (HKMT) inhibitors into drug-like starting points. This was achieved by exploring the structure–activity relationship (SAR) around two of these reported compounds.

Euchromatic histone methyltransferase (EHMT) 1 and EHMT2 are responsible for transferring methyl groups to lysine residues in histone tails. Dysregulation of these methylations has been implicated in cancers and other diseases, making these HKMTs interesting targets for drug development.

"Most reported compounds have three very basic sites, which are disadvantageous for cell permeability and limit cellular activity," explains Dr Ruben Leenders, the group leader overseeing this research. "To improve this activity, we explored the SAR around these compounds." By focusing on replacing the lysine-mimicking tail with more drug-like side chains, Mercachem succeeded in finding compounds that were more active in cellular assays. The assay results indicated an improvement in permeability and confirmed recent reports that it was possible to find compounds with significant selectivity towards EHMT1. These findings create an interesting starting point for a drug development program.

Leenders, Ruben et. al., Bioorganic & Medicinal Chemistry Letters, 2019 (17), 2516, Novel SAR for quinazoline inhibitors of EHMT1 and EHMT2


Find the article here   

Contact us