LDE225 Diphosphate (Synonyms: LDE 225 Diphosphate;NVP-LDE 225 Diphosphate;Erismodegib Diphosphate;LDE-225 Diphosphate) |
| رقم الكتالوجGC14169 |
A Smo antagonist
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1218778-77-8
Sample solution is provided at 25 µL, 10mM.
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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.
| 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. | |
| Cas No. | 1218778-77-8 | SDF | |
| المرادفات | LDE 225 Diphosphate;NVP-LDE 225 Diphosphate;Erismodegib Diphosphate;LDE-225 Diphosphate | ||
| Chemical Name | 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 | ||
| Formula | C26H32F3N3O11P2 | M.Wt | 681.49 |
| الذوبان | ≥ 27.85 mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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