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LDE225 (Diphosphate) 99%

LDE225 (Diphosphate)

源葉(MedMol)
S82394
1218778-77-8
C26H32F3N3O11P2
681.4885
品牌 貨號 產品規格 價格(RMB) 庫存（上海） 北京 武漢 南京 購買數量
源葉(MedMol) S82394-2mg 99% ￥250.00元 10 - - -
源葉(MedMol) S82394-5mg 99% ￥350.00元 10 - - -
源葉(MedMol) S82394-10mg 99% ￥500.00元 7 - - -
源葉(MedMol) S82394-50mg 99% ￥1000.00元 4 - - -
源葉(MedMol) S82394-100mg 99% ￥1700.00元 預計交期：2-3天 - - -
產品介紹 參考文獻 質檢證書(COA) 摩爾濃度計算器 相關產品

產品介紹

Sonidegib diphosphate (Erismodegib 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
產品描述： Sonidegib diphosphate (Erismodegib 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
靶點： IC50: 1.3 nM (mSmo), 2.5 nM (hSmo);Smo
體外研究：
The IC50 values for Sonidegib (NVP-LDE225) for the major human CYP450 drug metabolizing enzymes is greater than 10 μM. Sonidegib (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). Sonidegib 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)±Sonidegib 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 Sonidegib (10 nM; 0.78-fold and 100 nM; 0.73-fold, respectively (p<0.01)
體內研究：
Sonidegib (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, Sonidegib 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, Sonidegib 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, Sonidegib affords 51 and 83% regression, respectively. 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 Sonidegib (LDE225)+Nilotinib results in reduced white cell count (WCC) and reduces leukaemia development in secondary recipients compared to Sonidegib or Nilotinib alone.
參考文獻：
1. Pan S, et al. Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist. ACS Med Chem Lett. 2010 Mar 16;1(3):130-4. 2. Irvine DA, et al. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia. Sci Rep. 2016 May 9;6:25476.
溶解性： Soluble  in  DMSO、H2O
保存條件： -20℃
配置溶液濃度參考：
1mg 5mg 10mg
1 mM 1.467 ml 7.337 ml 14.674 ml
5 mM 0.293 ml 1.467 ml 2.935 ml
10 mM 0.147 ml 0.734 ml 1.467 ml
50 mM 0.029 ml 0.147 ml 0.293 ml
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參考文獻

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