UNC1215

UNC1215 is a potent and selective inhibitor for the methyllysine (Kme) reading domain function of L3MBTL3 with a K_d value of 120 nM and an IC₅₀ of 40 nM. UNC1215 has the potential to treat malignant brain tumor. IC50 & Target: IC50: 40 nM (L3MBTL3).
Kd: 120 nM (L3MBTL3). In Vitro: UNC1215 binds L3MBTL3 with a _d of 120 nM, competitively displacing mono- or dimethyllysine-containing peptides, and is greater than 50-fold more potent toward L3MBTL3 than other members of the MBT family while also demonstrating selectivity against more than 200 other reader domains examined. X-ray crystallography identified a unique 2:2 polyvalent mode of interaction between UNC1215 and L3MBTL3. In cells, UNC1215 is nontoxic and directly binds L3MBTL3 via the Kme-binding pocket of the MBT domains. UNC1215 increases the cellular mobility of GFP-L3MBTL3 fusion proteins, and point mutants that disrupt the Kme-binding function of GFP-L3MBTL3 phenocopy the effects of UNC1215 on localization^[1].