LDE225 DiphosphateSmo antagonist CAS# 1218778-77-8 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1218778-77-8 | SDF | Download SDF |
| PubChem ID | 45138699 | Appearance | Powder |
| Formula | C26H32F3N3O11P2 | M.Wt | 681.49 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | NVP-LDE 225 Diphosphate; Erismodegib Diphosphate | ||
| Solubility | DMSO : 100 mg/mL (146.74 mM; Need ultrasonic) H2O : 0.25 mg/mL (0.37 mM; Need ultrasonic) | ||
| Chemical Name | N-[6-[(2S,6R)-2,6-dimethylmorpholin-4-yl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamide;phosphoric acid | ||
| 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 | ||
| Standard InChIKey | RWIVSVMMGFFZIJ-VWDRLOGHSA-N | ||
| Standard InChI | 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+;; | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | LDE225 Diphosphate is a potent and selective Smo antagonist with IC50 of 1.3 nM and 2.5 nM for mouse and human Smo in binding assay, respectively.In Vitro:The IC50 values for NVP-LDE225 for the major human CYP450 drug metabolizing enzymes is greater than 10 μM[1]. LDE225 (Sonidegib), 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). LDE225 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)±LDE225 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 LDE225 (10 nM; 0.78-fold and 100 nM; 0.73-fold, respectively (p<0.01)[2].In Vivo:NVP-LDE225 is a weak base with a measured pKa of 4.2 and exhibits relatively poor aqueous solubility. In the subcutaneous Ptch+/-p53-/- medulloblastoma allograft mouse model, NVP-LDE225 demonstrated 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, NVP-LDE225 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, NVP-LDE225 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 LDE225 + Nilotinib results in reduced white cell count (WCC) and reduces leukaemia development in secondary recipients compared to LDE225 or Nilotinib alone[2]. References: | |||||
LDE225 Diphosphate Dilution Calculator
LDE225 Diphosphate Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.4674 mL | 7.3369 mL | 14.6737 mL | 29.3475 mL | 36.6843 mL |
| 5 mM | 0.2935 mL | 1.4674 mL | 2.9347 mL | 5.8695 mL | 7.3369 mL |
| 10 mM | 0.1467 mL | 0.7337 mL | 1.4674 mL | 2.9347 mL | 3.6684 mL |
| 50 mM | 0.0293 mL | 0.1467 mL | 0.2935 mL | 0.5869 mL | 0.7337 mL |
| 100 mM | 0.0147 mL | 0.0734 mL | 0.1467 mL | 0.2935 mL | 0.3668 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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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.
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