RN 1 dihydrochloride is a potent and selective inhibitor of LSD1 with IC50 value of 70 nM [1].
Lysine (K) -specific demethylase 1A (LSD1) is a flavin-dependent histone demethylase that demethylates mono- and di-methylated lysines and plays an important role in oocyte growth, embryogenesis and tissue-specific differentiation. LSD1 plays a role in acute myeloid leukemia (AML).
RN 1 dihydrochloride is a potent and selective LSD1 inhibitor. RN-1 inhibited monoamine oxidase MAO A and MAO B with IC50 values of 0.51 and 2.79 μM, respectively [1]. In baboon erythroid progenitor cells, RN-1 increased γ-globin expression [2].
In mice, RN-1 significantly impairs long-term memory but didn’t affect short-term memory [1]. In sickle cell disease (SCD) mice, RN-1 induced the expression of γ-globin and increased amounts of F cells and F reticulocytes [2]. In SCD mouse model, RN-1 induced HbF synthesis and increased amounts of mature erythrocytes and HbF-positive cells. Also, RN-1 reduced sickle cells and reticulocytes in the peripheral blood [3].
References:
[1]. Neelamegam R, Ricq EL, Malvaez M, et al. Brain-penetrant LSD1 inhibitors can block memory consolidation. ACS Chem Neurosci, 2012, 3(2): 120-128.
[2]. Rivers A, Vaitkus K, Ruiz MA, et al. RN-1, a potent and selective lysine-specific demethylase 1 inhibitor, increases γ-globin expression, F reticulocytes, and F cells in a sickle cell disease mouse model. Exp Hematol, 2015, 43(7): 546-553.e3.
[3]. Cui S, Lim KC, Shi L, et al. The LSD1 inhibitor RN-1 induces fetal hemoglobin synthesis and reduces disease pathology in sickle cell mice. Blood, 2015, pii: blood-2015-02-626259.