GSK2879552 dihydrochloride

GSK2879552 dihydrochloride an orally active, selective and irreversible inhibitor of lysine specific demethylase 1 (LSD1/KDM1A), with potential antineoplastic activity[1][2].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Demethylase

GSK2879552 inhibits KDM1A histone demethylase activity, inducing differentiation of sorafenib-resistant cells and attenuates stemness properties. GSK2879552 depresses the transcription of Wnt antagonists and downregulates β-catenin signaling activity in sorafenib-resistant cells[1]. Cell Viability Assay[2]. 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[1]. 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,Nanog and CD90, and elevated mRNA expression levels of differentiation markers Alb and Hnf4.

GSK2879552 (1.5 mg/kg, p.o.) treatment exhibits tumor growth inhibition in SCLC xenograft bearing mice[2]. Animal Model: NCI-H526 and NCI-H1417 xenografts[2]. 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.

[1]. Huang M, et al. Targeting KDM1A attenuates Wnt/β-catenin signaling pathway to eliminate sorafenib-resistant stem-like cells in hepatocellular carcinoma. Cancer Lett. 2017 Apr 2;398:12-21.

[2]. Mohammad HP, et al. A DNA Hypomethylation Signature Predicts Antitumor Activity of LSD1 Inhibitors in SCLC. Cancer Cell. 2015 Jul 13;28(1):57-69.