计算溶液所需的质量、体积或浓度。
为什么选择此级别
提供 ≥99% 纯度，适用于对基线干扰要求严格的色谱和分析工作流程。
储存与运输
2-8°C储存,干燥。低温运输 。请查阅批次 COA 获取详细规格。
质量文档
SDS、COA、产品数据表及规格说明书均可下载。可通过批号查询获取批次 COA。
文献证明
在色谱分析、有机合成和交叉偶联反应领域已被 0 篇同行评审文献引用。
概述
Sonidegib diphosphate (Erismodegib diphosphate) is a potent and selective Smo antagonist with IC 50 of 1.3 nM and 2.5 nM for mouse and human Smo in binding assay, respectively
In Vitro
The IC 50 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). MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Sonidegib (NVP-LDE225) is a weak base with a measured pK a 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay
CD34 + CP-CML cells are seeded in SFM alone±Sonidegib±Nilotinib and cultured for 24-72 h prior to assessment. Proliferation is measured using colorimetric assessment of BrDU incorporation. Proportion of viable cells versus those in early and late apoptosis is assessed by flow cytometry using annexin V-FITC and 7-amino-actinomycin D (7-AAD, Via-Probe solution). Cell cycle status is assessed using Ki67 (FITC) expression and 7-AAD incorporation. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal administration
Mice The transgenic EGFP + /SCLtTA/TRE-BCR-ABL mouse model is used to investigate the effect of Sonidegib treatment on CML LSC in vivo. Scl-tTa-BCR-ABL mice in the FVB/N background are crossed with transgenic GFP-expressing mice. Bone marrow cells are obtained 4 weeks post induction, GFP + cells are selected by flow cytometry and transplanted by tail vein injection (10 6 cells/mouse) into wild-type FVB/N recipient mice, irradiated at 900 cGy, generating a large cohort of mice with similar time of onset of leukemia. Blood samples obtained 4 weeks post transplantation confirmed a neutrophilic leukocytosis in recipient mice. Mice are treated with Nilotinib (50 mg/kg by gavage, daily), Sonidegib (80 mg/kg by gavage, daily), Sonidegib+Nilotinib, or with vehicle alone (control). After 3 weeks of treatment, animals are euthanised and marrow content of femurs and tibiae, spleen cells and blood obtained. Total white cell count (WCC), GFP-expressing WCC, myeloid cells, and GFP+ progenitors and stem cells are measured by flow cytometry. Survival is assessed in a subset of mice for 120d post discontinuation of treatment. Spleen and BM cells from a subset of mice in each arm are pooled and 5×10 6 cells/mouse (8 mice/condition) are transplanted into wild-type FVB/N recipient mice irradiated at 900 cGy. Engraftment is monitored by drawing peripheral blood (PB) every 4 weeks. The percentage of GFP + cells in PB is analyzed by flow cytometry. aladdin has not independently confirmed the accuracy of these methods. They are for reference only.
Form:Solid
IC50& Target:IC50: 1.3 nM (mSmo), 2.5 nM (hSmo)
规格
别名
索尼吉布二磷酸
英文别名
CHEBI:90864 | N-(6-((2R,6S)-2,6-Dimethylmorpholino)pyridin-3-yl)-2-methyl-4'-(trifluoromethoxy)-[1,1'-biphenyl]-3-carboxamide bis(phosphate) | Sonidegib phosphate | SONIDEGIB PHOSPHATE [USAN] | Erismodegib phosphate | NVP-LDE 225 diphosphateSonidegib diph
规格或纯度
≥99%
英文名称
Sonidegib diphosphate
生化机理
二磷酸索尼替吉布（Erismodegib diphosphate）是一种强效的选择性Smo拮抗剂，在结合试验中对小鼠和人类Smo的IC 50分别为1.3 nM和2.5 nM。
储存条件
2-8°C储存,干燥
运输条件
低温运输
作用类型
抑制剂
作用机制
平滑肌同源物抑制剂
纯度
≥99%
名称和识别符
分子类型
小分子
IUPAC Name
N-[6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamide;phosphoric acid
INCHI
1S/C26H26F3N3O3.2H3O4P/c1-16-14-32(15-17(2)34-16)24-12-9-20(13-30-24)31-25(33)23-6-4-5-22(18(23)3)19-7-10-21(11-8-19)35-26(27,28)29;2*1-5(2,3)4/h4-13,16-17H,14-15H2,1-3H3,(H,31,33);2*(H3,1,2,3,4)/t16-,17+;;
InChi Key
RWIVSVMMGFFZIJ-VWDRLOGHSA-N
Smiles
CC1CN(CC(O1)C)C2=NC=C(C=C2)NC(=O)C3=CC=CC(=C3C)C4=CC=C(C=C4)OC(F)(F)F.OP(=O)(O)O.OP(=O)(O)O
Isomeric SMILES
C[C@@H]1CN(C[C@@H](O1)C)C2=NC=C(C=C2)NC(=O)C3=CC=CC(=C3C)C4=CC=C(C=C4)OC(F)(F)F.OP(=O)(O)O.OP(=O)(O)O
PubChem CID
分子量
681.5
技术文档
高级数据
系统学分类
分类树（Taxonomy Tree）
| 界（kingdom) | 有机化合物 |
|---|---|
| 超类（Superclass) | 苯类化合物 |
| 类（Class) | 苯及其取代衍生物 |
| 亚类（Subclass） | 联苯及其衍生物 |
| 中间层级节点（Intermediate Tree Nodes） | 暂无 |
| 直接上位类(Direct Parent) | 联苯及其衍生物 |
| 其他上位类（Alternative Parents） | 邻甲苯酰胺类 苯甲酰胺类 苯氧基化合物 酚醚 苯甲酰衍生物 二烷基芳胺 氨基吡啶及其衍生物 有机磷酸及其衍生物 吗啉 咪唑内酰胺类 杂芳族化合物 三卤甲烷 仲羧酸酰胺 氧环化合物 氮杂环化合物 二烷基醚 有机氟化物 有机光子化合物 烷基氟化物 有机氧化物 碳氢化合物衍生物 |
| 分子骨架（Molecular Framework) | 芳香族杂单环化合物 |
| 取代基（Substituents） | 氟化烷基 - 烷基溴化物 - 氨基吡啶 - 芳香族杂单环化合物 - 氮杂环 - 苯甲酰胺 - 苯甲酸或衍生物 - 苯甲酰 - 联苯 - 羧酰胺基 - 羧酸衍生物 - 二烷基醚 - 二烷基芳基胺 - 乙醚 - 卤甲烷 - 杂芳香族化合物 - 烃衍生物 - 咪唑内酰胺 - Morpholine - 邻甲苯胺 - 有机硝基化合物 - 有机氧化物 - 有机氧化合物 - 有机磷酸酯 - 有机氟化物 - 有机卤化物 - 有机杂环化合物 - 有机氮化合物 - 有机氧化合物 - 有机氮化合物 - 氧杂环 - 氧杂吡嗪烷 - 苯酚醚 - 苯氧基化合物 - 吡啶 - 醛基 - 甲苯胺 - 甲苯 - 三卤甲烷 |
| 描述（Description） | 该化合物属于联苯及其衍生物类有机化合物。这类化合物含有两个通过C-C键连接的苯环。 |
| 外部描述符（External Descriptors） | 暂无 |
三维结构
交互式化学结构模型
化学和物理性质
溶解性
DMSO : 100 mg/mL (146.74 mM; Need ultrasonic) H2O : 0.25 mg/mL (0.37 mM; Need ultrasonic)
分子量
681.500 g/mol
XLogP3
氢键供体数Hydrogen Bond Donor Count
7
氢键受体数Hydrogen Bond Acceptor Count
16
可旋转键计数Rotatable Bond Count
5
精确质量Exact Mass
681.146 Da
单同位素质量Monoisotopic Mass
681.146 Da
拓扑极表面积Topological Polar Surface Area
219.000 Ų
重原子数Heavy Atom Count
45
形式电荷Formal Charge
0
复杂度Complexity
741.000
同位素原子数Isotope Atom Count
0
定义的原子立体中心计数Defined Atom Stereocenter Count
2
未定义的原子立体中心计数Undefined Atom Stereocenter Count
0
定义的键立体中心计数Defined Bond Stereocenter Count
0
未定义的键立体中心计数Undefined Bond Stereocenter Count
0
所有立体化学键的总数The total count of all stereochemical bonds
0
共价键合单元计数Covalently-Bonded Unit Count
3
质检证书（CoA,COO,BSE/TSE 和分析图谱)
C of A & Other Certificates(BSE/TSE, COO):
输入批号以搜索分析图谱:
技术文档和文章
溶液计算器
常见问题
本产品的纯度是多少？
本产品的化学纯度（含量）为 ≥99%。批次的具体数值以分析证书（COA）为准。
本产品应如何储存？
请于2–8 °C、干燥条件下保存。请与干燥剂一同密封保存，本品对湿气敏感。
本产品如何运输？
本产品采用湿冰冷藏运输。收货后请立即拆包，并按上述储存条件保存。
本产品的 CAS 号、分子式和分子量是多少？
本产品的 CAS 号为 1218778-77-8，分子式为 C26H32F3N3O11P2，分子量为 681.5 g/mol。InChIKey RWIVSVMMGFFZIJ-VWDRLOGHSA-N。
如何获取批次专用COA？
每个订单都会随附分析证书（COA），您也可以从账户订单历史中下载。如需订购前的COA，请联系您的客户代表，或使用PDP上的"申请COA"按钮——我们将提供代表性批次的COA。
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