GSK2879552

Description

GSK2879552 (1401966-65-5, free base) is potent, selective, and irreversible inhibitor of Lysine Demethylase 1 (LSD1) via covalent modification of the LSD1 cofactor FAD (Ki = 1.7 μM). It is selective for LSD1 over the closely related LSD2, MAO-A, MAO-B, and the FAD dependent enzymes D-amino acid oxidase and glutathione reductase. Tested against a panel of 165 cancer cell lines, GSK2879552 inhibited the proliferation of 9 small cell lung carcinoma lines and 20 AML cell lines.

Definition

ChEBI: GSK2879552 is a member of the class of piperidines that is piperidine substituted by (4-carboxyphenyl)methyl and {[(1R,2S)-2-phenylcyclopropyl]amino}methyl groups at positions 1 and 4, respectively. It is a potent and irreversible inhibitor of lysine specific demethylase 1 (LSD1, also known as KDM1A). It was under clinical investigation for the treatment of acute myeloid leukaemia and small cell lung carcinoma. It has a role as an EC 1.14.99.66 (lysine-specific histone demethylase 1A) inhibitor and an antineoplastic agent. It is a member of benzoic acids, a monocarboxylic acid, a member of piperidines, a member of cyclopropanes, a tertiary amino compound, a secondary amino compound and a member of benzenes.

in vitro

six days of gsk2879552 treatment resulted in potent anti-proliferative growth effects in 19 of 25 aml cell lines representing a range of aml subtypes. treating for longer time periods revealed sensitivity in all aml cell lines. aml blast colony forming ability was also inhibited in 4 of 5 bone marrow samples derived from primary aml patient samples [1].

in vivo

after 17 days of gsk2879552 treatment, control mice had 80% gfp+ cells in the bone marrow whereas treated mice had only 2.8% gfp positive cells, and the treated animals survived weeks beyond control mice [1].

References

1) Mohammad?et al.?(2015),?A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC; Cancer Cell?28?57