GSK2879552 is an orally available, irreversible inhibitor of lysine specific demethylase 1 (LSD1), with potential antineoplastic activity.

LSD1:

GSK2879552通过抑制KDM1A组蛋白去甲基化活性，诱导索拉非尼耐药细胞分化并减弱其干细胞特性。GSK2879552激活Wnt拮抗剂的转录并降低索拉非尼耐药细胞中的β-连环蛋白信号活性[1]。GSK2879552对D-氨基酸氧化酶有280倍的选择性，可以直接比较失活效率（KIapp=520 ± 170 μM, kinact=0.12 ± 0.01 min^-1, kinact/KIapp=2.3×10^-4 ± 1.31×10^-5 min^-1 μM^-1）。GSK2879552抑制了9/28小细胞肺癌（SCLC）系和20/29急性髓细胞性白血病（AML）系的生长，EC50为2-240 nM。

GSK2879552 (1.5 mg/kg, p.o.) 处理在携带SCLC异种移植瘤的小鼠中展示了肿瘤生长抑制效果。在NCI-H526和NCI-H1417携瘤小鼠中，分别观察到57%和83%的肿瘤生长抑制（TGI）。而NCI-H510与NCI-H69携瘤小鼠对GSK2879552的反应也表现出部分TGI（分别为38%和49%），但是在SHP77携瘤小鼠中未观察到显著的TGI。

Viable cells are measured in Cell Counting Kit-8 (CCK8) assay. Briefly, cells are cultured in a 96-well plate overnight at a density of 5×103 cells per well and treated with the indicated concentrations of sorafenib (0 μM, 40 μM or 80 μM) for 24 h. Subsequently, the cells are incubated with 10 μL CCK8 for 60 min at 37°C, 5% CO2. The absorbance of optical density at 450 nm (A450) is determined with Varioskan Flash.