Niclosamide-CAS 50-65-7-Calbiochem

C₁₃H₈Cl₂N₂O₄

327.12

MFCD00057597

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.
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.

Toxicity: Regulatory Review (Z)

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

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.

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

100

≥97% (HPLC)

solid

Calbiochem^®

OK to freeze
protect from light

pale yellow

DMSO: 2.5 mg/mL
ethanol: 5 mg/mL

ambient

2-8℃

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)

RJMUSRYZPJIFPJ-UHFFFAOYSA-N

1 g in Glass bottle
Packaged under inert gas

11 - Combustible Solids

WGK 2