GSK2879552 an orally active, selective and irreversible inhibitor of lysine specific demethylase 1 (LSD1/ KDM1A) , with potential antineoplastic activity
In Vitro
GSK2879552 inhibits KDM1A histone demethylase activity, inducing differentiation of Sorafenib (HY-10201)-resistant cells and attenuating stemness properties. GSK2879552 depresses the transcription of Wnt antagonists and downregulates β-catenin signaling activity in Sorafenib-resistant cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation Assay. Cell Line: 9/28 small cell lung carcinoma (SCLC) lines and 20/29 AML lines. Concentration: 0-10000 nM. Incubation Time: 6 days. Result: Inhibited cell proliferation. RT-PCR. Cell Line: Resistant HCC cells (PLC/PRF/5 and Huh7). Concentration: 0, 1, 2 μM. Incubation Time: 24 h. Result: Displayed reduced mRNA expression levels of stem cell markers, such as Lgr5, Sox9,\nNanog and CD90, and elevated mRNA expression levels of differentiation markers Alb and Hnf4.
In Vivo
GSK2879552 (1.5 mg/kg, p.o.) treatment exhibits tumor growth inhibition in SCLC xenograft-bearing mice. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: NCI-H526 and NCI-H1417 xenografts. Dosage: 1.5 mg/kg. Administration: PO daily for 25-35 days. Result: There was 57% and 83% tumor growth inhibition (TGI) in NCI-H526 and NCI-H1417 tumor bearing mice respectively. NCI-H510 and NCI-H69 tumor bearing mice also demonstrated partial TGI (38% and 49% respectively) in response to GSK2879552, while no significant TGI was observed for SHP77 bearing mice.
