LDE225 (NVP-LDE225,Erismodegib)
LDE225 is a potent and selective inhibitor of smoothened with IC50 values of 1.3nM in mouse and 2.5nM in human, respectively [1].
LDE225 is screened out from a high-throughput cell-based screen of in-house diversity combinatorial libraries and is developed to be an antagonist of Smo. Smo is an activator of the hedgehog(Hh) signaling pathway and aberrant activation links to tumorigenesis in several cancers. The antitumor efficacy of LDE225 has been evaluated in vivo. In the subcutaneous Ptch+/-p53-/- medulloblastoma allograft mouse model, LDE225 can significantly inhibit tumor growth at a dose of 5mg/kg/day. And in an orthotopic Ptch+/-p53-/- medulloblastoma allograft model, LDE225 is suggested to penetrate the blood-brain barrier in tumor-bearing animals and cause the tumor growth inhibition after 4 days of treatment. Additionally, the preclinical safety assays show that LDE225 has no genotoxicity and has good selectivity [1].
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, 1: 130–134.
- 1. Kowolik CM, Lin M, et al. "Attenuation of hedgehog/GLI signaling by NT1721 extends survival in pancreatic cancer." J Exp Clin Cancer Res. 2019 Oct 28;38(1):431. PMID:31661013
- 2. Coffman LG, Choi YJ, et al. "Human carcinoma-associated mesenchymal stem cells promote ovarian cancer chemotherapy resistance via a BMP4/HH signaling loop." Oncotarget. 2016 Feb 9;7(6):6916-32. PMID:26755648
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 485.5 |
| Cas No. | 956697-53-3 |
| Formula | C26H26F3N3O3 |
| Solubility | ≥24.3 mg/mL in DMSO; insoluble in H2O; ≥23 mg/mL in EtOH with ultrasonic |
| Chemical Name | N-[6-[(2S,6R)-2,6-dimethylmorpholin-4-yl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamide |
| SDF | Download SDF |
| 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
Cancer stem cells (CSCs) |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
10 μM, 48 hours (for apoptosis induction) 10 μM, 7 days (for cell viability inhibition) |
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Applications |
LDE225 induced apoptosis in a dose-dependent manner. Treatment of prostate CSCs resulted in an increase in the expression of cleaved caspase-3 and PARP. LDE225 inhibited cell viability in primary and secondary spheroids in a dose-dependent manner. |
| Animal experiment: [1] | |
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Animal models |
NOD/SCID IL2Rγnull mice injected with human prostate CSCs |
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Dosage form |
Intraperitoneal injection, 20mg/kg body weight, three times per week for 4 weeks |
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Applications |
NVP-LDE-225 had no effect on body weight of mice. Interestingly, NVP-LDE-225 inhibited CSC tumor growth, as demonstrated by the significant reduction in tumor weight. |
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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] Nanta R, Kumar D, Meeker D, et al. NVP-LDE-225 (Erismodegib) inhibits epithelial–mesenchymal transition and human prostate cancer stem cell growth in NOD/SCID IL2Rγ null mice by regulating Bmi-1 and microRNA-128. Oncogenesis, 2013, 2(4): e42. |
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| Description | LDE225 is a potent and selective antagonist of Smoothened (Smo) with IC50 values of 2.5 nM and 1.3 nM for human Hedgehog and mouse Hedgehog, respectively. | |||||
| Targets | human Hedgehog | mouse Hedgehog | ||||
| IC50 | 2.5 nM | 1.3 nM | ||||
Quality Control & MSDS
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Chemical structure
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