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Purity: ≥98%
Chloroquine HCl is reported to be highly effective in combating SARS-CoV-2 (COVID-19, CoronaVirus, or the COVID-19 pandemic) infection in vitro. It acts as a potent autophagy and toll-like receptors (TLRs) inhibitor, and a 4-aminoquinoline anti-malarial medication used to prevent and to treat malaria in areas where malaria is known to be sensitive to its effects. It is also an anti-rheumatoid agent, also acting as an ATM activator. Chloroquine diphosphate has been reported as an adjuvant for radiation and chemotherapy for inducing cell autophagy to anti-cancer cells proliferation or metastasis. The mechanism of chloroquine diphosphate inducing cells autophagy is arresting cells in G1, up-regulates the expression of p27 and p53 while down-regulates the expression of CDK2 and cyclin D1.
| Targets |
Antiviral; Plasmodium; SARS-COV-2; Malaria; TLRs; HIV-1
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| ln Vitro |
The release of IL-12p70 is inhibited and the Th1 priming capacity of activated human monocyte-derived Langerhans-like cells (MoLC) is reduced by 20 μM of chloroquine diHCl. Primed CD4+ T cells release more IL-17A when exposed to chloroquine disalt (20 μM), which also promotes IL-1-induced IL-23 production in MoLC [1]. In both normoxic and hypoxic settings, MMP-9 mRNA expression is inhibited in parental MDA-MB-231 cells by 25 μM of chloroquine diHCl. The effects of chloroquine dihydrochloride on the mRNA expression of MMP-2, MMP-9, and MMP-13 are dose-, cell-, and hypoxia-dependent [2]. Using IRS-954 or chloroquine dihydrochloride to inhibit TLR7 and TLR9 dramatically decreased HuH7 cell proliferation in vitro [3]. At low micromolar doses (EC50=1.13 μM), chloroquine dihydrochloride (0.01-100 μM; 48 hours) efficiently inhibits viral infection (vero E6 cells infected with SARS-CoV-2). By raising the endosomal pH necessary for virus/cell fusion and interfering with the glycosylation of SARS-CoV cell receptors, chloroquine dihydrochloride inhibits viral infection [4].
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| ln Vivo |
In an orthotopic mouse model, chloroquine dihydrochloride (80 mg/kg, i.p.) does not stop triple-negative MDA-MB-231 cells from growing, regardless of how much TLR9 is expressed [2]. In murine xenograft models, TLR7 and TLR9 inhibition with IRS-954 or chloroquine dihydrochloride markedly reduced tumor growth. Additionally, in the DEN/NMOR rat model, chloroquine greatly reduces the development of HCC [3].
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| Enzyme Assay |
Chloroquine suppressed matrix metalloproteinase (MMP)-2 and MMP-9 mRNA expression and protein activity, whereas MMP-13 mRNA expression and proteolytic activity were increased. Despite enhancing TLR9 mRNA expression, chloroquine suppressed TLR9 protein expression in vitro.[2]
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| Cell Assay |
In this study, we investigated the effect of CHQ on human monocyte-derived Langerhans-like cells (MoLC) and dendritic cells (MoDC) in response to IL-1β. The presence of CHQ reduced IL-12p70 release in both subsets, but surprisingly increased IL-6 production in MoDC and IL-23 in MoLC. Importantly, CHQ-treated MoLC promoted IL-17A secretion by CD4(+) T cells and elevated RORC mRNA levels, whereas IFN-γ release was reduced. The dysregulation of IL-12 family cytokines in MoLC and MoDC occurred at the transcriptional level. Similar effects were obtained with other late autophagy inhibitors, whereas PI3K inhibitor 3-methyladenine failed to increase IL-23 secretion. The modulated cytokine release was dependent on IL-1 cytokine activation and abrogated by a specific IL-1R antagonist. CHQ elevated expression of TNFR-associated factor 6, a common intermediate in IL-1R and TLR-dependent signaling. Accordingly, treatment with Pam3CSK4 and CHQ enhanced IL-23 release in MoLC and MoDC. CHQ inhibited autophagic flux, confirmed by increased LC3-II and p62 expression, and activated ERK, p38, and JNK MAPK, but only inhibition of p38 abrogated IL-23 release by MoLC. Thus, our findings indicate that CHQ modulates cytokine release in a p38-dependent manner, suggesting an essential role of Langerhans cells and dendritic cells in CHQ-provoked psoriasis, possibly by promoting Th17 immunity.[1]
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| Animal Protocol |
Control and TLR9 siRNA MDA-MB-231 cells (5×105 cells in 100 μl) were inoculated into the mammary fat pads of four-week-old, immune-deficient mice (athymic nude/nu Foxn1; Harlan Sprague Dawley, Inc., Indianapolis, IN, USA). Treatments were started seven days after tumor cell inoculation. The mice were treated daily either with intraperitoneal (i.p.) chloroquine (80 mg/kg) or vehicle (PBS). The animals were monitored daily for clinical signs. Tumor measurements were performed twice a week and tumor volume was calculated according to the formula V = (π / 6) (d1 × d2)3/2, where d1 and d2 are perpendicular tumor diameters (9). The tumors were allowed to grow for 22 days, at which point the mice were sacrificed and the tumors were dissected for a final measurement. Throughout the experiments, the animals were maintained under controlled pathogen-free environmental conditions (20–21ºC, 30–60% relative humidity and a 12-h lighting cycle). The mice were fed with small-animal food pellets (Harlan Sprague Dawley) and supplied with sterile water ad libitum. The experimental procedures were reviewed and approved by the University of Alabama at Birmingham Institutional Animal Care and Use Committee.[2]
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| References |
[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. [5]. Savarino A, et al. The anti-HIV-1 activity of chloroquine. J Clin Virol. 2001;20(3):131-135. |
| Molecular Formula |
C18H28CL3N3
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|---|---|
| Molecular Weight |
392.793
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| Exact Mass |
391.135
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| Elemental Analysis |
C, 55.04; H, 7.19; Cl, 27.08; N, 10.70
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| CAS # |
3545-67-3
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| Related CAS # |
Chloroquine phosphate;50-63-5;Chloroquine;54-05-7;Chloroquine-d5;1854126-41-2;Chloroquine-d5 diphosphate;1854126-42-3
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| PubChem CID |
83820
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| LogP |
6.5
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| tPSA |
28.16
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| SMILES |
CC(NC1=CC=NC2=CC(Cl)=CC=C12)CCCN(CC)CC.[H]Cl.[H]Cl
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| InChi Key |
PCFGECQRSMVKCC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H26ClN3.2ClH/c1-4-22(5-2)12-6-7-14(3)21-17-10-11-20-18-13-15(19)8-9-16(17)18/h8-11,13-14H,4-7,12H2,1-3H3,(H,20,21)2*1H
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| Chemical Name |
N4-(7-chloroquinolin-4-yl)-N1,N1-diethylpentane-1,4-diamine dihydrochloride
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| Synonyms |
Chloroquine hydrochloride Aralen hydrochlorideNSC 14050 NSC-14050 NSC14050 Aralen HCl
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5459 mL | 12.7294 mL | 25.4589 mL | |
| 5 mM | 0.5092 mL | 2.5459 mL | 5.0918 mL | |
| 10 mM | 0.2546 mL | 1.2729 mL | 2.5459 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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