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LDE225 (NVP-LDE225,Erismodegib)

In stock
Catalog No.
B2266
Smoothened inhibitor,potent and selective
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$55.00
In stock
5mg
$50.00
In stock
10mg
$70.00
In stock
50mg
$150.00
In stock
100mg
$250.00
In stock
200mg
$480.00
In stock

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Background

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.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt485.5
Cas No.956697-53-3
FormulaC26H26F3N3O3
Solubility≥24.3mg/mL in DMSO
Chemical NameN-[6-[(2S,6R)-2,6-dimethylmorpholin-4-yl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamide
SDFDownload SDF
Canonical SMILESCC1CN(CC(O1)C)C2=NC=C(C=C2)NC(=O)C3=CC=CC(=C3C)C4=CC=C(C=C4)OC(F)(F)F
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor 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.

Protocol

Cell experiment: [1]

Cell lines

Cancer stem cells (CSCs)

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.

Reaction Conditions

10 μM, 48 hours (for apoptosis induction) 10 μM, 7 days (for cell viability inhibition)

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]

Animal models

NOD/SCID IL2Rγnull mice injected with human prostate CSCs

Dosage form

Intraperitoneal injection, 20mg/kg body weight, three times per week for 4 weeks

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.

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.

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.

Biological Activity

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        

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