Fanny L. Cherblanc

TL;DR: It is concluded that chaetocin, or related natural products, are not fit for application as selective chemical probes of HKMT function, and the disulfide bridge of the ETP unit is central to chaetOCin’s HKMT inhibitory activity by a nonspecific mechanism.

TL;DR: It is demonstrated that dual inhibition of EZH2 and EHMT2 is more effective at eliciting biological responses of gene transcription and cancer cell growth inhibition compared to inhibition of single HKMTs, and the first dual EZh2-EHMT1/2 substrate competitive inhibitors that are functional in cells are reported.

TL;DR: It is revealed that only the structurally unique ETP core is required for inhibition, and such inhibition is time-dependent and irreversible (in the absence of DTT), ultimately resulting in protein denaturation.

TL;DR: This review will give a perspective on the current status of natural product epigenetic modulators, highlighting the limitations, challenges and opportunities for currently identified molecules, as well as potential strategies for novel compound discovery moving forward.

TL;DR: Crystallographic studies on histone lysine methyl transferases provide insights into their mechanism and specificity crucial for the design and development of small-molecule inhibitors, believed to be a highly promising epigenetic target which has yet to be clinically exploited.