Uses
SGC0946 is a potent DOT1L methyltransferase inhbiitor used in the treatment of leukemia seen effectively in vitro.
Biological Activity
sgc 0946 is a potent small-molecule inhibitor of protein methyltransferase (pmt) dot1l, a unique protein lysine methyltransferase (pkmt) catalyzing the methylation of histone h3 on lysine 79 (h3k79), with the half maximal inhibition concentration ic50 value of 0.3 nm [1].as a brominated analogue of epz004777, sgc 0946 exhibits substantially increased cellular inhibitory potency than its predecessor, where sgc 0946 reduces the methylation of h3k79 in both mcf10a (ic50: 8.8 nm) and a431 (ic50: 2.65 nm) cells compared with epz004777 (ic50: 84 nm and 264 nm respectively). this greatly increased cellular inhibitory potency of sgc 0946 can be attributed to lower off-rate and to improved cell permeability [1].
Biochem/physiol Actions
SGC0946 is a potent and selective inhibitor of Histone H3-lysine79 (H3K79) methyltransferase DOT1L with an IC50 of 0.3 nM in a radioactive enzyme assay, and over 100-fold selectivity for DOT1L over other histone methyltransferases. In cell studies, SGC0946 reduces H3K79 dimethylation with an IC50 of 2.6 nM in A431 cells and 8.8 nM in MCF10A cells. SGC0946 was found to selectively kills cells transformed with the MLL-AF9 fusion oncogene in an in vitro model of leukemia. For full characterization details, please visit the SGC0946 probe summary on the Structural Genomics Consortium (SGC) website.SGC0649 is the negative control for the active probe, SGC0946. To request a sample of the negative control from the SGC, click here.To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc
