CAS NO: | 1218778-77-8 |
包装 | 价格(元) |
10 mM * 1 mL in DMSO | 电议 |
5mg | 电议 |
10mg | 电议 |
50mg | 电议 |
100mg | 电议 |
200mg | 电议 |
500mg | 电议 |
生物活性 | Sonidegib diphosphate (Erismodegib diphosphate) is a potent and selectiveSmoantagonist withIC50of 1.3 nM and 2.5 nM for mouse and humanSmoin binding assay, respectively[1]. | ||||||||||||||||
IC50& Target | IC50: 1.3 nM (mSmo), 2.5 nM (hSmo)[1] | ||||||||||||||||
体外研究 (In Vitro) | The IC50values for Sonidegib (NVP-LDE225) for the major human CYP450 drug metabolizing enzymes is greater than 10 μM[1]. 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,GLI1is significantly downregulated following exposure to Sonidegib (10 nM; 0.78-fold and 100 nM; 0.73-fold, respectively (p<0.01)[2]. | ||||||||||||||||
体内研究 (In Vivo) | Sonidegib (NVP-LDE225) is a weak base with a measured pKaof 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[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 Sonidegib (LDE225)+Nilotinib results in reduced white cell count (WCC) and reduces leukaemia development in secondary recipients compared to Sonidegib or Nilotinib alone[2]. | ||||||||||||||||
Clinical Trial | |||||||||||||||||
分子量 | 681.49 | ||||||||||||||||
性状 | Solid | ||||||||||||||||
Formula | C26H32F3N3O11P2 | ||||||||||||||||
CAS 号 | 1218778-77-8 | ||||||||||||||||
运输条件 | Room temperature in continental US; may vary elsewhere. | ||||||||||||||||
储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) | ||||||||||||||||
溶解性数据 | In Vitro: DMSO : 100 mg/mL(146.74 mM;Need ultrasonic) H2O : 0.25 mg/mL(0.37 mM;Need ultrasonic) 配制储备液
* 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百
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