CAS 50-65-7|Niclosamide

Introduction：Basic information about CAS 50-65-7|Niclosamide, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Niclosamide BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
MUTATION DATA
5. Safety Information
6. Customs
7. Articles51
8. Synonyms

Common Name	Niclosamide
CAS Number	50-65-7	Molecular Weight	327.120
Density	1.6±0.1 g/cm3	Boiling Point	424.5±45.0 °C at 760 mmHg
Molecular Formula	C₁₃H₈Cl₂N₂O₄	Melting Point	225-230ºC
MSDS	ChineseUSA	Flash Point	210.5±28.7 °C
Symbol	GHS09	Signal Word	Warning

Names

Name	niclosamide
Synonym	More Synonyms

Niclosamide BiologicalActivity

Description	Niclosamide is an inhibitor of STAT3 with IC50 of 0.25 μM in HeLa cells and inhibits DNA replication in a cell-free assay.
Related Catalog	Signaling Pathways >>JAK/STAT Signaling >>STATSignaling Pathways >>Stem Cell/Wnt >>STATResearch Areas >>Infection
Target	STAT3:0.25 μM (IC50, in HeLa cells)
In Vitro	Niclosamide is an inhibitor of STAT3, inhibiting STAT3-mediated luciferase reporter activity with an IC50 of 0.25 μM in HeLa cells. Niclosamide (1 μM) inhibits the EGF-induced nuclear translocation of STAT3 in Du145 cells. Niclosamide (< 2 μM) dose dependently inhibits the transcription of STAT3 downstream genes in Du145 cells. Niclosamide (< 10 μM) induces G0/G1 arrest and apoptosis of Du145 cancer cells in a dose dependent manner[1]. Niclosamide can block SARS-CoV replication at a micromolar concentration in Vero E6 cells infected with SARS-CoV[2]. Niclosamide (< 7.5 μM) promotes Frizzled1 endocytosis, downregulates Dishevelled-2 protein, and inhibits Wnt3A-stimulated beta-catenin stabilization and LEF/TCF reporter activity in U2OS cells[3]. Niclosamide inhibits the TNF-induced NF-κB reporter activity in a dose- and time-dependent manner in U2OS cells. Niclosamide (125 nM) inhibits NF-κB activation induced by p65, IKKα, IKKβ, IKKγ, and TAK1 in U2OS cells. Niclosamide (< 500 nM) completely block the time- and dose-dependent TNFα-induced alteration of the NF-κB-DNA complex in HL-60 cells. Niclosamide (< 10 nM) inhibits constitutive NF-κB activation in U266 cells. Niclosamide inhibits TNF-induced degradation of IκBα and relocation of p65 in a dose- and time-dependent manner in HL-60, Molm13, or AML primary cells. Niclosamide (500 nM) causes decrease in TNF-induced NF-κB-dependent gene products involved in cell survival in HL-60 cells. Niclosamide also inhibits the growth and induces robust apoptosis of AML cells associated with decreased Mcl-1 and XIAP levels and increased intracellular ROS levels[4].
In Vivo	Niclosamide (40 mg/kg/d, i.p.) suppresses the growth of xenografted AML cells in nude mice bearing HL-60 xenograft tumors[4].
Kinase Assay	All of the protein kinases are expressed either in Sf9 insect cells or in E.coli as recombinant GST-fusion proteins or His-tagged proteins. A radiometric protein kinase assay is used for measuring the kinase activity of the 22 protein kinases. Briefly, for each protein kinase, 50 μL reaction cocktail containing 60 mM HEPES-NaOH, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/mL PEG20000, 1 μM [γ-33P]-ATP, Niclosamide, adequate amount of enzyme and its substrate. The PKC-alpha assay additionally contain 1 mM Ca2, 4 mM EDTA, 5 μg/mL phosphatidylserine and 1 μg/mL 1, 2-Dioleyl-glycerol. The reaction cocktails are incubated at 37°C for 60 minutes and stop with 50 μL 2% (v/v) H3PO4. Incorporation of 33Pi is determined with a microplate scintillation counter. The activities and the IC50 values are calculated using Quattro Workflow V2.28.
Cell Assay	Cells are plated in 96-well culture plates with cell density of 3-4 ×103 cells/well and treat with Niclosamide by adding 100 μL medium containing Niclosamide of various concentrations on the second day. After 72-hour's treatment, MTT is added to each well and incubated for additional 4-5 hours, and the absorbance is measured on a microplate reader at 570 nm. Cell growth inhibition is evaluated as the ratio of the absorbance of the sample to that of the control. The results are representative of at least 3 independent experiments.
Animal Admin	Male nu/nu BALB/c mice are used in the assay. HL-60 cells are inoculated s.c. on the flanks of 4- to 6-wk-old mice. Tumors are measured every other day with use of calipers. Mice bearing HL-60 xenografts are randomized to receive treatment with normal saline (control) or p-niclosamide for 15 days (n=7 animals each). Tumor volumes are calculated by the following formula: a2×b×0.4, where a is the smallest diameter and b is the diameter perpendicular to a. After mice are euthanized, xenografts are dissected, weighed, or preserved.
References	[1]. Ren, X., et al., Identification of niclosamide as a new small-molecule inhibitor of the STAT3 signaling pathway. ACS Medicinal Chemistry Letters, 2010. 1(9): p. 454-459. [2]. Wu CJ, et al. Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide. Antimicrob Agents Chemother. 2004 Jul;48(7):2693-6. [3]. Chen, M., et al., The anti-helminthic niclosamide inhibits Wnt/Frizzled1 signaling. Biochemistry, 2009. 48(43): p. 10267-74. [4]. Jin, Y., et al. Antineoplastic mechanisms of niclosamide in acute myelogenous leukemia stem cells: inactivation of the NF-kappaB pathway and generation of reactive oxygen species. Cancer Res, 2010. 70(6): p. 2516-27.

Chemical & Physical Properties

Density	1.6±0.1 g/cm3
Boiling Point	424.5±45.0 °C at 760 mmHg
Melting Point	225-230ºC
Molecular Formula	C₁₃H₈Cl₂N₂O₄
Molecular Weight	327.120
Flash Point	210.5±28.7 °C
Exact Mass	325.986115
PSA	95.15000
LogP	5.41
Vapour Pressure	0.0±1.0 mmHg at 25°C
Index of Refraction	1.709
InChIKey	RJMUSRYZPJIFPJ-UHFFFAOYSA-N
SMILES	O=C(Nc1ccc([N+](=O)[O-])cc1Cl)c1cc(Cl)ccc1O

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: VN8400000

CHEMICAL NAME :: Salicylanilide, 2',5-dichloro-4'-nitro-

CAS REGISTRY NUMBER :: 50-65-7

LAST UPDATED :: 199712

DATA ITEMS CITED :: 17

MOLECULAR FORMULA :: C13-H8-Cl2-N2-O4

MOLECULAR WEIGHT :: 327.13

WISWESSER LINE NOTATION :: WNR CG DMVR BQ EG

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2500 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 250 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 7500 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: >1 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 300 mg/kg

SEX/DURATION :: male 5 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Cytogenetic analysis

TYPE OF TEST :: Sister chromatid exchange

MUTATION DATA

TEST SYSTEM :: Rodent - mouse

DOSE/DURATION :: 300 mg/kg/5D (Continuous)

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 204,269,1988

Safety Information

Symbol	GHS09
Signal Word	Warning
Hazard Statements	H400
Precautionary Statements	P273
Personal Protective Equipment	Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter
Hazard Codes	Xi
RIDADR	UN 3077 9/PG 3
WGK Germany	2
RTECS	VN8400000
Hazard Class	9.0
HS Code	2924299090

Customs

HS Code	2924299090
Summary	2924299090. other cyclic amides (including cyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

Articles51

The salicylanilide derivatives inhibit signal transducer and activator of transcription 3 pathways in A549 lung cancer cells.

Anticancer Drugs 27 , 41-7, (2015)

The signal transducer and activator of transcription 3 (STAT3) is constitutively activated in certain cancer cells. Therefore, blocking the aberrant activity of STAT3 in tumor cells is a validated the...

Taenia solium: Development of an Experimental Model of Porcine Neurocysticercosis.

PLoS Negl. Trop. Dis. 9 , e0003980, (2015)

Human neurocysticercosis (NC) is caused by the establishment of Taenia solium larvae in the central nervous system. NC is a severe disease still affecting the population in developing countries of Lat...

Phase I and phase II reductive metabolism simulation of nitro aromatic xenobiotics with electrochemistry coupled with high resolution mass spectrometry.

Anal. Bioanal. Chem 406(28) , 7253-60, (2014)

Electrochemistry combined with (liquid chromatography) high resolution mass spectrometry was used to simulate the general reductive metabolism of three biologically important nitro aromatic molecules:...

Synonyms

2',5-Dichloro-4'-nitrosalicylanilide

2’,5-dichloro-4’-nitrosalicylanilide

iomesan

nasemo

NICLOCIDE

hl2447

Niclosamide

clonitralid

EINECS 200-056-8

iomezan

bay2353

lintex

MFCD00057597

sulqui

5-Chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide

mato

fenasal

5-Chlor-N-(2-chlor-4-nitrophenyl)-2-hydroxybenzolcarboxamid

Benzamide, 5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxy-

b2353

Recommended......