LDE225 Diphosphate
(Synonyms: LDE 225 Diphosphate;NVP-LDE 225 Diphosphate;Erismodegib Diphosphate;LDE-225 Diphosphate) 目录号 : GC14169
A Smo antagonist
Cas No.:1218778-77-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
primary CD34+ CP-CML cells |
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Preparation method |
The solubility of this compound in DMSO is > 27.85 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
10 nM, 100 nM, 72 hours |
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Applications |
LDE225 (10 nM, 100 nM, 72 hours) inhibited downstream Hh signaling in primary CD34+ CP-CML cells. LDE225 (0.5-100 nM, 72h) significantly reduced colony forming cell (CFC) re-plating efficiency of primitive human CP-CML cells. LDE225 (10 nM) alone or in combination with nilotinib (5 μM) significantly reduced LTC-IC numbers in primary CD34+ CP-CML samples. |
| Animal experiment [1]: | |
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Animal models |
CP-CML murine model, BCR-ABL expressing mice |
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Dosage form |
80 mg/kg by gavage, daily |
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Application |
Treatment of Scl-tTa-BCR-ABL mice with LDE225+nilotinib resulted in inhibition of Gli1 in CP-CML BM LTHSC. LDE225 in combination with nilotinib on human CML LSC was capable of engrafting immunodeficient mice. LDE225+nilotinib administration significantly reduced leukaemia stem and progenitor cells in the spleen of BCR-ABL expressing mice. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Irvine D A, Zhang B, Kinstrie R, et al. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia[J]. Scientific reports, 2016, 6: 25476. | |
IC50: 1.3 and 2.5 nM for Mouse and Human Smo
LDE225 is a potent and selective smoothened antagonist. Smoothened (Smo) is a 7-pass transmembrane protein functioning as the key activator of the hedgehog (Hh) signaling pathway. Hh signaling is tightly controlled during cellular differentiation, proliferation, and embryonic morphogenesis. Hh signaling has been linked to tumorigenesis in several cancers.
In vitro: LDE225 was found to selectively bind to the Hedgehog (Hh)-ligand cell surface receptor Smo, which might result in the suppression of the Hh signaling pathway and, therefore, the inhibition of tumor cells in which this pathway was abnormally activated [1].
In vivo: In the subcutaneous medulloblastoma allograft mouse model, LDE225 demonstrated dose-related antitumor activity after 10 days of oral administration of a suspension. At a dose of 5 mg/kg/ day qd, LDE225 inhibited tumor growth significantly, corresponding to a T/C value of 33%. When dosed at 10 and 20 mg/kg/day qd, LDE225 afforded 51 and 83% regression, respectively [1].
Clinical trial: In a phase I study, it was found that LDE225 had an acceptable safety profile in patients with advanced solid tumors and exhibited antitumor activity in advanced BCC and relapsed medulloblastoma, both of which were associated with hedgehog pathway strongly, as shown by gene expression [2].
References:
[1] Shifeng Pan,Xu Wu,Jiqing Jiang et al. Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist. ACS Med Chem Lett. 2010 Jun 10; 1(3): 130–134.
[2] Rodon J,Tawbi HA,Thomas AL,Stoller RG,Turtschi CP,Baselga J,Sarantopoulos J,Mahalingam D,Shou Y,Moles MA,Yang L,Granvil C,Hurh E,Rose KL,Amakye DD,Dummer R,Mita AC. A phase I, multicenter, open-label, first-in-human, dose-escalation study of the oral smoothened inhibitor Sonidegib (LDE225) in patients with advanced solid tumors. Clin Cancer Res.2014 Apr 1;20(7):1900-9.
| Cas No. | 1218778-77-8 | SDF | |
| 别名 | LDE 225 Diphosphate;NVP-LDE 225 Diphosphate;Erismodegib Diphosphate;LDE-225 Diphosphate | ||
| 化学名 | N-[6-[(2S,6R)-2,6-dimethylmorpholin-4-yl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamide;phosphoric acid | ||
| Canonical 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 | ||
| 分子式 | C26H32F3N3O11P2 | 分子量 | 681.49 |
| 溶解度 | ≥ 27.85 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.4674 mL | 7.3369 mL | 14.6737 mL |
| 5 mM | 0.2935 mL | 1.4674 mL | 2.9347 mL |
| 10 mM | 0.1467 mL | 0.7337 mL | 1.4674 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。