The lysine-specific demethylase (LSD1) is a Flavin-dependent amine oxidase that selectively removes one or two methyl groups from histone H3 at the Lys4 position. Along with histone deacetylases 1 and 2, LSD1 is involved in epigenetically silencing gene expression, and has been implicated as a potential therapeutic target in cancer and other diseases[2].
GSK2879552 2HCl is an orally available, irreversible, inhibitor of lysine specific demethylase 1 (LSD1), with potential antineoplastic activity[3]. A proliferation screen of cell lines representing a number of tumor types indicated that small cell lung carcinoma (SCLC) was sensitive to LSD1 inhibition. The SCLC lines that undergo growth inhibition in response to GSK2879552 exhibit DNA hypomethylation of a signature set of probes suggesting this may be used as a predictive biomarker of activity[4]. The mice were treated with either vehicle or GSK2879552 (5 mg/kg) for 4 weeks with the sizes of the tumors monitored every other day. The tumors in mice treated with GSK2879552 are not only much smaller but also weigh much lesser. The effect of GSK2879552 in the patient-derived xenograft (PDX) model used metastatic BCa tissues and found that GSK2879552 is capable of inhibiting the growth of PDX significantly. Furthermore, the results of IHC showed the levels of Ki67 and Bcl-2 in xenografts derived from either cancer cells or PDX were also inhibited by GSK2879552[5].
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