LDE225 Diphosphate

Cas No.:	1218778-77-8
Chemical Name:	Sonidegib phosphate
Synonyms:	N-[6-[(2S,6R)-2,6-dimethylmorpholin-4-yl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamide,phosphoric acid;UNII-W421AI34UW;Erismodegib Diphosphate;LDE225 Diphosphate;Sonidegib phosphate;NVP-LDE 225 Diphosphate;CS-1175;;LDE 225 phosphate;rel-N-[6-[(2R,6S)-2,6-Dimethyl-4-morpholinyl]-3-pyridinyl]-2-methyl-4'-(trifluoromethoxy)-[1,1'-biphenyl]-3-carboxamide phosphate (1:2);LDE225 (Diphosphate);Sonidegib phosphate;LDE225 Diphosphate;sonidegib diphosphate;Sonidegib (diphosphate);W421AI34UW;Sonidegib phosphate [USAN:INN];Odomzo (TN);sonidegib bisphosphate;Sonidegib phosphate (USAN);AOB87343;BCP11860;3888AH;C26H26F3N3O3.2H3O4P;SB16677;(1,1'-Biphenyl)-3-carboxamide, N-(6-((2R,6S)-
SMILES:	N1(C[C@H](C)O[C@H](C)C1)C1=CC=C(C=N1)NC(=O)C1C=CC=C(C2C=CC(=CC=2)OC(F)(F)F)C=1C.P(O)(O)(O)=O.P(O)(O)(O)=O
Formula:	C26H32F3N3O11P2
M.Wt:	681.49
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Erismodegib diphosphate (LDE225 diphosphate) is a potent and selective Smo antagonist with IC50 of 1.3 nM and 2.5 nM for mouse and human Smo in binding assay, respectively.
In Vivo:	Erismodegib (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, Erismodegib demonstrates 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, Erismodegib significantly inhibits tumor growth, corresponding to a T/C value of 33% (p<0.05 as compared to vehicle controls). When dosed at 10 and 20 mg/kg/day qd, Erismodegib affords 51 and 83% regression, respectively[1]. 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 Erismodegib (LDE225)+ Nilotinib results in reduced white cell count (WCC) and reduces leukaemia development in secondary recipients compared to Erismodegib or Nilotinib alone[2].
In Vitro:	The IC50 values for Erismodegib (NVP-LDE225) for the major human CYP450 drug metabolizing enzymes is greater than 10 μM[1]. Erismodegib (LDE225), 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). Erismodegib 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)±Erismodegib 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 Erismodegib (10 nM; 0.78-fold and 100 nM; 0.73-fold, respectively (p<0.01)[2].