生物活性

• 靶点	Hedgehog IC50:5μM

• 描述The zinc-finger transcription factors Gli1, Gli2, and Gli3 are the prime transcriptional effectors of Hedgehog (Hh) signaling pathway involved in several malignancies, at least one constitutive activation of which is critical importance for cancer development. GANT61 is a downstream inhibitor of Hedgehog signaling (below smo and Sufu) with IC50 value of about 5μM for the inhibition of Hedgehog reporter activity in Shh-L2 cells, which may target on Gli1. A significant decreased expression of Hh target genes, Gli1 and Hip1 on mRNA level can be observed in Sufu^-/- cells treated with 10μM GANT61 for 3 days, while a slight increase of Gli1 could be observed at 2μM. Consistent with the inhibition of Hedgehog signaling, treatment with 5μM GANT 61 for 48h led to a significant reduction of GLI1 and a slight reduction of PTCH expression in both 22Rv1 and PANC1 cells, as well as a cell proliferative inhibition of about 50%. Subcutaneous injection with 50mg/kg GANT 61 for 16 days, daily at the beginning 3 days and every other day on the rest, could suppress tumor growth of female BALB/c nude mice subcutaneously injected with 22Rv1 cells, with a significant decreased expression of PTCH on mRNA level observed. The pancreatic CSCs migration and invasion could be dose-dependently inhibited by 1, 5, 10μM GANT 61 for 24 or 48h, and the decreased expression of c-Myc, Nanog, Sox-2 and Oct-4 on mRNA level could be observed at 36h.

• 动物研究
  剂量	Nude Mice: 25 mg/kg[3] (s.c.), 50 mg/kg[4] (p.o.)
  给药途径	s.c., p.o.