Sonidegib (Erismodegib) is a potent and selectiveSmoantagonist withIC₅₀of 1.3 nM and 2.5 nM for mouse and humanSmoin binding assay, respectively^[1].

IC50: 1.3 nM (mSmo), 2.5 nM (hSmo)^[1]

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].

Sonidegib (NVP-LDE225) is a weak base with a measured pK_aof 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].

485.50

Solid

C₂₆H₂₆F₃N₃O₃

956697-53-3

Room temperature in continental US; may vary elsewhere.

DMSO : 50 mg/mL(102.99 mM;Need ultrasonic)

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。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

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
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (5.15 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.15 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: 2.5 mg/mL (5.15 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (5.15 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (5.15 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.15 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。