OG-L002 is an effective and selective LSD1 inhibitor (IC50: 20 nM), showing 69- and 36-fold selectivity over MAO-A and MAO-B, respectively.

LSD1:20 nM

OG-L002 potently inhibits HSV IE gene expression in both HeLa and HFF cells with IC50 of ~10 μM and ~3 μM , respectively. OG-L002 treatment (50 μM ) results in the reduced production of progeny virus with no significant toxicity in HeLa or HFF cells. OG-L002 (50 μM ) increases the levels of repressive chromatin on viral IE gene promoters. In addition, OG-L002 also represses the expression of hCMV IE genes and adenovirus E1A gene. [1]

OG-L002 (6 to 40 mg/kg) represses HSV primary infection in a dose-dependent manner in a mouse model. Moreover, OG-L002 also represses HSV reactivation from latency in a mouse ganglion explant model. [1]

LSD1 demethylation assay: Human recombinant LSD1 protein is incubated with dimethylated H3K4 peptide as the substrate in the presence of various concentrations of lead compound inhibitors (0 to 75 μM ) or control tranylcypromine. The demethylase activity is measured by the release of Water2 produced during the catalytic process, using the Amplex red peroxide/peroxidase-coupled assay kit. Each reaction is done in triplicate. The maximum LSD1 demethylase activity is obtained in the absence of inhibitor and corrected for background fluorescence. The Ki (IC50) of OG-L002 is calculated as half-maximal activity.

HeLa or HFF cells are treated with the indicated concentrations of saponin (positive control) or compound OG-L002 for 12 hours. Cytotoxicity is determined using conditions recommended by the manufacturer and expressed as ratios to the cytotoxicity of the DMSO control.(Only for Reference)