Biological Activity
hlcl-61 is a prmt5 inhibitor.aberrant methylation of protein arginine residues mediated by protein arginine methyltransferase (prmt) enzymes is reported to be linked to cancer. prmts are a family of proteins with 11 known members catalyzing the transfer of methyl group(s) to the guanidine nitrogen atoms of peptide arginine residues. prmt5 has multiple substrates including histones and other non-chromatin proteins and has been gained attention for cancer therapy.
in vitro
in previous study, hlcl-61 showed no inhibitory activity against prmt1, prmt4, and type ii prmt family members, therefore demonstrating its specificity for prmt5. hlcl-61 also showed effective inhibition of symmetric arginine dimethylation of histones h3 and h4, starting at 12 h posttreatment and persisting for 48 h. moreover, the treatment of aml cell lines and primary blasts with hlcl-61 led to the decrease of cell viability. in addition, hlcl-61-treated aml cell lines and patient samples had induction of differentiation as demonstrated by dose-dependent increases in the expression of cd11b. furthermore, prmt5 inhibition caused by hlcl-61 treatment led to a decrease in mv4-11 cells [1].
