481909

Niclosamide

A salicylanilide anthelmintic drug that acts as a potent and selective Stat3- and Wnt-signaling pathway inhibitor.

• Synonym(s): Niclosamide, 5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxy-benzamide, mTOR Inhibitor IX, Autophagy Inducer III, STAT3 Inhibitor XV, Wnt Pathway Inhibitor XIII
• Empirical Formula (Hill Notation): C₁₃H₈Cl₂N₂O₄
• CAS Number: 50-65-7
• Molecular Weight: 327.12
• MDL number: MFCD00057597
• UNSPSC Code: 12352200

Properties

• Quality Level: 100
• assay: ≥97% (HPLC)
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: pale yellow
• solubility: DMSO: 2.5 mg/mL; ethanol: 5 mg/mL
• shipped in: ambient
• storage temp.: 2-8°C
• InChI: 1S/C13H8Cl2N2O4/c14-7-1-4-12(18)9(5-7)13(19)16-11-3-2-8(17(20)21)6-10(11)15/h1-6,18H,(H,16,19)
• InChI key: RJMUSRYZPJIFPJ-UHFFFAOYSA-N

Description

General description

A cell-permeable salicylanilide that, in addition to its well-known antihelmintic efficacy and use in tapeworm treatment, acts as a mammalian mTORC1, but not mTORC2, signaling inhibitor mechanistically distinct from rapamycin, causing MCF-7 autophagy activation under nutrient-rich conditions (by 15-fold with 4h 10 M treatment), SH-SY5Y lysosome redistribution (10 M for 8 h), and dissipation/clearance of ubiquinated protein aggregates upon proteasome inhibition in a reversible, time- and dose-dependent manner. Likely a direct consequence of autophagy activation, Niclosamide is demonstrated to induce Wnt-independent Frizzled1 endocytosis (t_1/2 = 2.4 h; effective conc. <2 M) and Dishevelled-2 downregulation (IC₅₀ ~1 M), effectively preventing Wnt3a from stimulating HEK293 cellular LEF/TCF transcription activity (IC₅₀ = 0.5 M TOPFlash reporter assays). Unrelated to its autophagy induction activity, Niclosamide is also shown to inhibit Stat3 signaling (IC₅₀ = 0.25 M in HeLa-based pLucTKS3 reporter assays) by suppressing the phosphorylation of Jak1 Tyr1022/1023 (2 h treatment at 0.5 to 2.0 M in Du145 cultures) and Stat3 Tyr705 (by >90% after 24 h treatment at 2 and 5 M, respectively, in Du145 and HeLa cultures), without affecting the phosphorylation of Stat1 Tyr701, Stat3 Ser727, Stat5 Tyr694, or Jak2 Tyr1007/1008.

A cell-permeable salicylanilide that, in addition to its well-known antihelmintic efficacy, acts as a mammalian mTORC1, but not mTORC2, signaling inhibitor mechanistically distinct from rapamycin. Likely a direct consequence of autophagy activation, Niclosamide is demonstrated to induce Wnt-independent Frizzled1 and Dishevelled-2 downregulation. Unrelated to its autophagy induction activity, Niclosamide is also shown to inhibit Stat3 signaling (IC₅₀ = 0.25 M in HeLa reporter assays). Efficiently inhibits breast cancer stem-like cells in vitro and in vivo.

Packaging

Packaged under inert gas

Warning

Toxicity: Regulatory Review (Z)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C. Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Wang, Y.C., et al. 2013. PLoS ONE8, e74538.
Chen, W., et al. 2010. Am. J. Physiol. Gastrointest. Liver Physiol.299, G293.
Gies, E., et al. 2010. PLoS ONE5, e14410.
Ren, X., et al. 2010. ACS Med. Chem. Lett.1, 454.
Chen, M., et al. 2009. Biochemistry48, 10267.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 2
• flash_point_f: Not applicable
• flash_point_c: Not applicable