GSK2879552 + azacitidine

GSK2879552 + azacitidine is a combination therapy under investigation primarily for hematologic malignancies such as high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML)[1][3][4][5][7][9]. **GSK2879552** is a potent, selective, irreversible small molecule inhibitor of **lysine-specific demethylase 1 (LSD1, also known as KDM1A)**. Inhibition of LSD1 alters gene expression by changing the methylation state of histone proteins, resulting in derepression of tumor-suppressor genes, induction of differentiation, and decreased proliferation in malignant cells[1][2][3][6]. **Azacitidine** is a hypomethylating agent (a DNA methyltransferase inhibitor) that induces DNA hypomethylation, reactivating silenced genes, and promotes differentiation or apoptosis in abnormal blood cells. The mechanistic overlap between GSK2879552 and azacitidine forms the rationale for combining them, with the hypothesis that dual epigenetic targeting could enhance efficacy in MDS and AML, especially in cases refractory to prior hypomethylating agents[1][9]. Both drugs are administered in cycles: GSK2879552 is given orally once daily, and azacitidine is administered intravenously or subcutaneously at standard doses[1].

Brand names

VidazaOnureg

Other names

LSD1 inhibitor GSK2879552 + azacitidine