GNT61

GANT61 is an inhibitor for GLI1 as well as GLI2-induced transcription. GANT61 inhibits the DNA binding ability of GLI1. GANT61 inhibits hedgehog signaling with IC50 of 5 μM, displays selectivity over other pathways, such as TNF signaling/NFκB activation, glucocorticoid receptor gene transactivation, and the Ras–Raf–Mek–Mapk cascade. GANT61 efficiently inhibited in vitro tumor cell proliferation in a GLI-dependent manner. ^[1] GANT61 induces apoptosis in chronic lymphocytic leukemia cells (CLL), but not in normal B lymphocytes. ^[2] GANT61 induces robust cytotoxicity and abolishs the clonogenicity in human colon carcinoma cell lines. ^[3] GANT61 induces inhibition of DNA replication in early S-phase in human colon carcinoma cell lines, leading to DNA damage signaling involving an ATM–Chk2 axis and induction of cell death. ^[4] GANT61 (30 μM) causes growth arrest and apoptosis in acute myeloid leukemia (AML) cells. ^[5]