Probe

GSK-LSD1

GSK-LSD1 (trans-racemic)
MW 216.3
FW  289.2 (di-HCl)

Lysine specific demethylase 1 (LSD1) is a histone demethylase found in various transcriptional co-repressor complexes. LSD1 is involved in ES cell differentiation, hematopoiesis, and has been described as having a role in Acute Myeloid Leukemia (AML). GlaxoSmithKline has developed an irreversible, mechanism based inhibitor of LSD1, GSK-LSD1, and has made this available as a chemical probe as part of the SGC epigenetics initiative. GSK-LSD1 inhibits LSD1 with an IC₅₀ of 16 nM and is > 1000 fold selective over other closely related FAD utilizing enzymes (i.e. LSD2, MAO-A, MAO-B).  GSK-LSD1 induces gene expression changes in cancer cell lines (average EC₅₀ < 5 nM) and inhibits cancer cell line growth (average EC₅₀ < 5 nM). 

LSD-1 at 10 µM showed no activity against 55 human recombinant receptors in the CEREP ExpresSProfile selectivity/specificity profile (GPCR, transporters, ion channels), except 5-HT1A (49% inhibition) 5-HT transporter (74% inhibition) and dopamine transporter (39 % inhibition).