Chloroquine

Chloroquine is an antimalarial and anti-inflammatory agent widely used to treat malaria and rheumatoid arthritis. Chloroquine is a autophagy and toll-like receptors (TLRs) inhibitor. Chloroquine is highly effective in the control of SARS-CoV-2 (COVID-19) infection in vitro (EC50=1.13 μM)[1][2][3][4].

Signaling Pathways >> Immunology/Inflammation >> Toll-like Receptor (TLR)

Research Areas >> Cancer

Signaling Pathways >> Anti-infection >> HIV

Signaling Pathways >> Anti-infection >> SARS-CoV

Signaling Pathways >> Autophagy >> Autophagy

TLRs, HIV, SARS-CoV-2, Autophagy[1][2][3][4]

Chloroquine (CHQ, 20 μM) inhibits IL-12p70 release and reduces Th1-priming capacity of activated human monocyte-derived Langerhans-like cells (MoLC). Chloroquine (20 μM) enhances IL-1–induced IL-23 secretion in MoLC and subsequently increases IL-17A release by primed CD4+ T cells[1]. Chloroquine (25 μM) suppresses MMP-9 mRNA expression in normoxia and hypoxia in parental MDA-MB-231 cells. Chloroquine has cell-, dose- and hypoxia-dependent effects on MMP-2, MMP-9 and MMP-13 mRNA expression[2]. TLR7 and TLR9 inhibition using IRS-954 or chloroquine significantly reduces HuH7 cell proliferation in vitro[3]. Chloroquine (0.01-100μM; 48 hours) potently blocked virus infection (vero E6 cells infected with SARS-CoV-2) at low-micromolar concentration (EC50=1.13 μM). Chloroquine blocks virus infection by increasing endosomal pH required for virus/cell fusion, as well as interfering with the glycosylation of cellular receptors of SARS-CoV[4].

Chloroquine (80 mg/kg, i.p.) does not prevent the growth of the triple-negative MDA-MB-231 cells with high or low TLR9 expression levels in the orthotopic mouse model[2]. TLR7 and TLR9 inhibition using IRS-954 or chloroquine significantly inhibits tumour growth in the mouse xenograft model. HCC development in the DEN/NMOR rat model is also significantly inhibited by Chloroquine[3].

[1]. Said A, et al. Chloroquine promotes IL-17 production by CD4+ T cells via p38-dependent IL-23 release by monocyte-derived Langerhans-like cells. J Immunol. 2014 Dec 15;193(12):6135-43.

[2]. Tuomela J, et al. Chloroquine has tumor-inhibitory and tumor-promoting effects in triple-negative breast cancer. Oncol Lett. 2013 Dec;6(6):1665-1672.

[3]. Mohamed FE, et al. Effect of toll-like receptor 7 and 9 targeted therapy to prevent the development of hepatocellular carcinoma. Liver Int. 2014 Jul 2. doi: 10.1111/liv.12626.

[4]. Colson P, et al. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020;55(4):105932.

MOLECULAR FORMULA :

C18-H26-Cl-N3

MOLECULAR WEIGHT :

319.92

WISWESSER LINE NOTATION :

T66 BNJ EMY1&3N2&2 IG

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

24 mg/kg/12D-I

TOXIC EFFECTS :

Brain and Coverings - changes in surface EEG Behavioral - hallucinations, distorted perceptions Behavioral - changes in motor activity (specific assay)

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

110 mg/kg

TOXIC EFFECTS :

Cardiac - change in rate Cardiac - other changes Gastrointestinal - nausea or vomiting

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

3600 mg/kg/3Y

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - visual field changes Gastrointestinal - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

86 mg/kg

TOXIC EFFECTS :

Cardiac - change in rate Cardiac - other changes Gastrointestinal - nausea or vomiting

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

20 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - diplopia Behavioral - coma Vascular - BP elevation not characterized in autonomic section

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

37593 ug/kg

TOXIC EFFECTS :

Brain and Coverings - other degenerative changes Behavioral - convulsions or effect on seizure threshold Cardiac - change in rate

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

330 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

102 mg/kg

TOXIC EFFECTS :

Gastrointestinal - other changes

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

190 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 :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

60 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 :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

311 mg/kg

TOXIC EFFECTS :

Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

66 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 :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

150 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 :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

21600 ug/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 :

Intramuscular

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

71 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 :

Subcutaneous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

75 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 :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

8 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

20 mg/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

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

560 mg/kg/14D-I

TOXIC EFFECTS :

Behavioral - food intake (animal) Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

9800 mg/kg/35W-C

TOXIC EFFECTS :

Behavioral - food intake (animal) Blood - changes in leukocyte (WBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

360 mg/kg/30D-I

TOXIC EFFECTS :

Behavioral - tremor Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

420 mg/kg

SEX/DURATION :

female 1-42 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

1155 mg/kg

SEX/DURATION :

female 6-39 week(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Effects on Newborn - other postnatal measures or effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

840 mg/kg

SEX/DURATION :

female 1-84 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - abortion

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

10500 mg/kg

SEX/DURATION :

female 1-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - hepatobiliary system

TYPE OF TEST :

Specific locus test

TYPE OF TEST :

Sex chromosome loss and nondisjunction

MUTATION DATA

TYPE OF TEST :

DNA damage

TEST SYSTEM :

Mammal - species unspecified Lymphocyte

DOSE/DURATION :

500 umol/L

REFERENCE :

BBACAQ Biochimica et Biophysica Acta. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1947- Volume(issue)/page/year: 561,77,1979 *** REVIEWS *** IARC Cancer Review:Animal Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 13,47,1977 IARC Cancer Review:Human No Adequate Data IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 13,47,1977 IARC Cancer Review:Group 3 IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,56,1987 TOXICOLOGY REVIEW PLMJAP Pahlavi Medical Journal. (Shiraz, Iran) V.1-9, 1970-78. Volume(issue)/page/year: 6,160,1975 TOXICOLOGY REVIEW 32XPAD "Teratology," Berry, C.L., and D.E. Poswillo, eds., New York, Springer, 1975 Volume(issue)/page/year: -,49,1975 TOXICOLOGY REVIEW FNSCA6 Forensic Science. (Lausanne, Switzerland) V.1-11, 1972-78. For pub lisher information, see FSINDR. Volume(issue)/page/year: 2,67,1973 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4820 No. of Facilities: 7 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 103 (estimated) No. of Female Employees: 52 (estimated)