GSK-LSD1 (hydrochloride)

GSK-LSD1 (hydrochloride) is a potent, irreversible and mechanism-based inhibitor of LSD1 [1].

Lysine specific demethylase 1 (LSD1) is a histone H3K4me1/2 demethylase existed in many transcriptional co-repressor complexes. LSD1 mediates H3K4 demethylation, causes a repressive chromatin environment which results in gene expression silence and has been shown to play a role in hematopoietic differentiation. It has been demonstrated that LSD1 is overexpressed in multiple tumor types [2].

In vitro: GSK-LSD1 inhibited the activity of LSD1 with an IC50 of 16 nM that is >1,000-fold selective over the closely related FAD-utilizing enzymes, such as LSD2, MAO-A, and MAO-B. GSK-LSD1 inhibited cell proliferation by inducing gene expression changes in various cancer cell lines, the EC50s were < 5 nM [1].

In vivo: In mice bearing LX44 or LX48, daily treatment with 1.5 mg/kg GSK-LSD1 showed 69% and 74% TGI, respectively [3].

References:
[1] Epigenetics probes collection.  (2014).
[2] Smitheman K, Cusan M, Liu Y, et al.  Inhibition of LSD1 for the treatment of cancer[J]. 2015.
[3] Mohammad H P, Smitheman K N, Kamat C D, et al.  A DNA hypomethylation signature predicts antitumor activity of LSD1 inhibitors in SCLC[J]. Cancer Cell, 2015, 28(1): 57-69.