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LDE225 (Sonidegib) diphosphate is a potent and selective Hedgehog signaling pathway inhibitor (Smoothened antagonist) reduces melanoma growth in vitro and in vivo. NVP-LDE225 was potent in reducing cell proliferation and inducing tumor growth arrest in vitro and in vivo, respectively.Pharmacologic inhibition of BRAF(V600E) in human melanoma cell lines resulted in decreased expression of GLI1 thus demonstrating interaction of SHH-GLI and MAPK pathways. Inhibition of SHH-GLI pathway by the novel small molecule inhibitor of smoothened NVP-LDE225 was followed by inhibition of cell growth and induction of apoptosis in human melanoma cell lines, interestingly with both BRAF(V600E) and BRAF(Wild Type) status.LDE225 significantly reduces the tumor volume by 95.7% in Rip1-Tag2 mice. LDE225 prolongs survival in Rip1Tag2 mice. LDE225 decreases expression of stromal markers in the LDE225-treated mice.
Technological University Dublin. 2022 Dec.
Development of novel anticancer agents targeting G protein coupled receptor: GPR120
LDE225 (Sonidegib) diphosphate purchased from AbMole
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Source | BMC Cancer (2017). Figure 4. LDE225 |
| Method | western blot | |
| Cell Lines | BALB/c nude mice | |
| Concentrations | 80 mg/kg | |
| Incubation Time | 41 day | |
| Results | Western blotting showed increased amounts of GLI1 in tumors from animals treated with 177Lu-octreotate monotherapy and combination treatment, and increased amounts of GLI2 in tumors from the combination therapy group, compared with controls |
| Molecular Weight | 681.49 |
| Formula | C26H32F3N3O11P2 |
| CAS Number | 1218778-77-8 |
| Solubility (25°C) | DMSO ≥ 60 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related Smo Products |
|---|
| GDC-0449 (Vismodegib)
GDC-0449 (Vismodegib) is a potent and specific hedgehog pathway inhibitor with IC50 values of 1.4 and 3.0μM for inhibition of ABCG2 and Pgp respectively. |
| Purmorphamine
Purmorphamine is a small molecule Hh agonist which activates the hedgehog pathway by directly binding to SMO. |
| BMS-833923
BMS-833923 is an orally bioavailable Smoothened antagonist. |
| Halcinonide
Halcinonide is a high potency corticosteroid used in topical preparations as an anti-inflammatory agent. |
| SANT-1
SANT-1 directly binds to Smoothened (Smo) receptor with Kd of 1.2 nM and inhibits Smo agonist effects with IC50 of 20 nM. |
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