Smo

681.5

DMSO: ≥ 31 mg/mL

Powder

The IC50 values for NVP-LDE225 for the major human CYP450 drug metabolizing enzymes is greater than 10 μM. LDE225 (Sonidegib), a small molecule, clinically investigated SMO inhibitor, used alone and in combination with Nilotinib, inhibits the Hh pathway in CD34+ chronic phase (CP)-chronic myeloid leukaemia (CML) cells, reducing the number and self-renewal capacity of CML leukaemia stem cell (LSC). LDE225 interacts directly with SMO, in a similar fashion to cyclopamine, to reduce expression of downstream Hh signaling targets. Primary CD34+ CP-CML cells are cultured in serum free media (SFM)±LDE225 for 6, 24 and 72 hours (h). At 72 h, while there is variability between the biological samples, GLI1 is significantly downregulated following exposure to LDE225 (10 nM; 0.78-fold and 100 nM; 0.73-fold, respectively (p.

NVP-LDE225 is a weak base with a measured pKa of 4.2 and exhibits relatively poor aqueous solubility. In the subcutaneous Ptch+/-p53-/- medulloblastoma allograft mouse model, NVP-LDE225 demonstrated dose-related antitumor activity after 10 days of oral administration of a suspension of the diphosphate salt. At a dose of 5 mg/kg/day qd, NVP-LDE225 significantly inhibits tumor growth, corresponding to a T/C value of 33% (p. Bone marrow cells and spleen cells from a subset of treated mice are transplanted into secondary recipient mice. Transplantation of either bone marrow (BM) or spleen cells from mice treated with LDE225 + Nilotinib results in reduced white cell count (WCC) and reduces leukaemia development in secondary recipients compared to LDE225 or Nilotinib alone.

NVP-LDE225,LDE225,LDE 225 Diphosphate; NVP-LDE 225 Diphosphate; Erismodegib Diphosphate; LDE-225 Diphosphate

C₂₆H₂₆F₃N₃O₃.2H₃PO₄

1218778-77-8