Sonidegib diphosphate (LDE225 diphosphate) is a selective antagonist of Smo that inhibits murine Smo (IC50:1.3 nM) and human Smo (IC50:2.5 nM).

Smo:2.5 nM (IC50), Smo (mouse):1.3 nM (IC50)

METHODS: Sonidegib diphosphate (LDE225 diphosphate) (10, 100nM, 72 hours) was treated in CD34 CP-CML cells and its effect on GLI1 expression in CD34 CP-CML cells was assessed.
RESULTS No changes in GLI1 were observed in CD34 CP-CML cells at 6 and 24 h; at 72 h, GLI1 was significantly downregulated (10 nM; 0.78-fold and 100 nM; 0.73-fold). [2]

METHODS: A transgenic EGFP/SCLtTA/TRE-BCR-ABL mouse model was used, and mice were treated with nilotinib (50 mg/kg, gavage, daily, 3 weeks), Sonidegib diphosphate (LDE225 diphosphate) (80 mg / kg, gavage, daily, 3 weeks), Sonidegib diphosphate (LDE225 diphosphate) + nilotinib, or carrier alone (control) treatment, to study the effects of Sonidegib diphosphate (LDE225 diphosphate) treatment on CML LSC in vivo.
RESULTS The cohort treated with Sonidegib diphosphate (LDE225 diphosphate) had a small, non-significant incremental reduction in mean body weight; Sonidegib diphosphate (LDE225 diphosphate) alone reduced splenic LTHSC but did not significantly reduce GMP and CMP ; Sonidegib diphosphate (LDE225 diphosphate) + nilotinib significantly reduced GMP, CMP, and LTHSC in the spleen. in contrast, in the BM of mice treated with Sonidegib diphosphate (LDE225 diphosphate), nilotinib, or the combination there were no significant changes in the amounts of GMP, CMP and LTHSC. [2]