Lysine-specific demethylase 1 (LSD1) belongs to the family of flavin adenine dinucleotide (FAD)-dependent amine oxidases that include monoamine oxidases (MAOs). RN-1 is a potent, irreversible inhibitor of LSD1 (IC50 = 70 nM). It is much less effective against MAO-A and MAO-B (IC50s = 0.51 and 2.8 μM, respectively). Following intraperitoneal administration, RN-1 penetrates the blood-brain barrier and distributes in mice to a brain/plasma exposure ratio of 88.9. It blocks long-term but not short-term memory in mice. RN-1 also induces cytotoxicity in ovarian cancer cell lines and induces fetal hemoglobin synthesis while reducing disease pathology in sickle cell mice.
