Please Note: Due to coronavirus restrictions, budget cuts and civil protests, UPS delivery guarantees have been withdrawn, and USPS shipments may be subject to extra delays and/or skipped tracking scans. (For the latest UPS service updates, please check at ups.com). We are working hard to minimize delays; but we ask customers to take into account the risk of up to 3 extra days of domestic shipment transit time (or up to 5-15 days extra international transit time). Thanks to all for your understanding during this challenging period!

Chloroquine Phosphate, ≥99%

You need to have an approved account to purchase this product.

Quinine analogue with antimalarial, anti-inflammatory, antibacterial, and antiviral effects.

WE ARE DONATING THIS COMPOUND TO CREDENTIALED HEALTH PROFESSIONALS
AND INSTITUTIONALLY AFFILIATED RESEARCH TEAMS.  PLEASE CONTACT US FOR
DETAILS ON APPLYING TO RECEIVE COMPOUND ON A NON-COMMERCIAL BASIS.
 
Chemical NameN(4)-(7-Chloro-4-quinolinyl)-N(1),N(1)-diethyl-1,4-pentanediamine, phosphate (1:2)
CAS Number50-63-5
Purity≥99%
Molecular Weight515.9 g/mol
Molecular FormulaC18H26ClN3 ·2 H3PO4
PubChem CID64927
SMILESCCN(CC)CCCC(C)NC1=C2C=CC(=CC2=NC=C1)Cl.OP(=O)(O)O.OP(=O)(O)O

Prices will be visible after login and/or successful approval.

From $3.98

Precaution and Disclaimer:

This Material is Sold For Research Use Only. Terms of Sale Apply. Not for Human Consumption, nor Medical, Veterinary, or Household Uses.

Chloroquine is a compound originally discovered through modification of Quinine's structure, and has proven to bear antimalarial, anti-inflammatory, antibacterial, and antiviral effects.

Chemical Information:

Chemical Name:

4-N-(7-chloroquinolin-4-yl)-1-N,1-N-diethylpentane-1,4-diamine;phosphoric acid

CAS Number:

54-63-5

Purity:

≥99%

Molecular Weight:

515.9 g/mol

Melting Point:

193 – 198 °C

Molecular Formula:

C18H32ClN3O8P2

Synonyms:

Chloroquine diphosphate; Chloroquine phosphate; 50-63-5; Aralen phosphate; Arechin; Delagil; Tanakan; Chloroquine bis(phosphate); Resochin; Chingaminum; Alermine; Chingamin phosphate; H-Stadur; Aralen diphosphate; Avloclor; Khingamin; Miniquine; Quingamine; Tanakene; Chlorochin diphosphate; Chloroquin diphosphate; Tanakan (antimalarial); Gontochin phosphate; dl-Chloroquine diphosphate; Chloroquine diphosphate salt; NSC 14050; Ipsen 225; CCRIS 1554; EINECS 200-055-2

PubChem CID:

64927

SMILES:

O=C(OCC)CCCCCCNC(C1=CC=C(I)C=C12)C3=CC=CC=C3N(C)S2(=O)=O 

Technical Information:

Application:

Chloroquine is an antimalarial drug currently being researched for its potential antiviral effects on HIV and for combating RNA viruses, including SARS-CoV-2.

Appearance:

White to off-white crystalline powder

Physical State:

Solid

Solubility:

Very slightly soluble in alcohols

Storage / Stability:

Store at room temperature or cooler, in a sealed airtight container, protected from heat, light and humidity.  Stable for at least two years when stored as above, protected from light.

Background:

Chloroquine diphosphate is a compound developed through structural modification of quinine and has traditionally been used as an antimalarial drug, albeit with incompletely understood mechanisms of action and potentially severe side effects, particularly with overdose of more than 1 gram or extended consumption of more than 100 grams cumulative, that can in some cases limit the quantity or durationof use.[i] It is often saved for difficult cases that do not respond to usual treatments.

Chloroquine is currently being deprecated from antimalarial therapy due to the widespread emergence of chloroquine-resistant strains. However, it is now increasingly valued for its antiviral and antibacterial benefits, especially in light of its simultaneous effects on immume and inflammatory response, which may synergistically improve benefits in vivo.

By virtue of its immune modulating effects, Chloroquine is sometimes used for its anti-inflammatory effects, such as to help deal with rheumatoid arthritis. Chloroquine may also be used alongside chemotherapy treatments.  More recently Chloroquine has drawn attention for its antiviral properties - and Chloroquine phosphate is currently recommended for use to physicians in China for the treatment of COVID-19 pneumonia.

Notwithdstanding the above descriptions of Chloroquine's use as a pharmaceutical product, please note that this compound is sold by NewMind only for non clinical scientific research and analytical chemistry purposes, not as a pharmacuetical drug nor for any other type of human consumption or medical use.  This chemical is for research & laboratory use only. Your order may be cancelled if you do not ship to a registered business address, laboratory or research facility. Before your order is processed, we may need to further confirm your business and organization information, and your TAX ID or EIN# may be required before shipment of Chloroquine Phosphate is approved.  Orders not meeting our requirements may be subject to cancellation and refund.

For in vitro research. at concentrationsof 200 mg/ml (PBS, pH 5.0), Chloroquine can be used to dissociate antigen-antibody complexes, without denaturing red blood cell antigens. At a lower concentration of 100 µM, it can be used for DNA transfection by intercalating into DNA and improving transfection efficiency.


Pharmacology:

  • Absorption: Rapid and almost completely
  • Distribution: Widely distributed into body tissues
  • Protein binding: 55%
  • Metabolism: Partially hepatic to main metabolite, desethylchloroquine
  • Excretion: Urine (≥50% as unchanged drug); acidification of urine increases elimination

Chloroquine has a pK of 8.5 at a physiological pH level. It has a lysosomotropic character, which is believed to be important for its antimalarial effects.


Modes of action:

Chloroquine has several mechanisms of action through which it exerts its antimalarial, anti-inflammatory, and antiviral effects.

Its antimalarial effects are best understood as they have been studied in the most detail. Chloroquine is capable of interrupting the malaria parasite by undermining its capacity to protect itself from its own toxic metabolite – heme, which is formed through the parasite’s metabolism of hemoglobin.

By preventing the parasite from metabolizing toxic heme into non-toxic hemozoin, the compound causes a heme build-up. It then binds to heme and forms a highly toxic complex, which causes lysis of the infected cell.

As a note; recent research suggests that the previously understood antimalarial mechanisms may be partially or fully incorrect.

In terms of Chloroquine’s antiviral effects, studies have indicated that it increases the endosomal pH required for virus-cell fusion, while also interfering with the glycosylation of cellular receptors of RNA viruses, including SARS-CoV-2.

Chloroquine/ Hydroxychloroquine can impair the replication of several viruses by interacting with pH balance, the endosome-mediated viral entry, or the late stages of replication of enveloped viruses.

  1. Interference with viral replication through pH-effects

… Chloroquine was shown to inhibit the infection by influenza type A and type B and adenovirus in target cells. It has been demonstrated that [chloroquine] inhibits the replication of the human viruses H1N1 and H3N2, as well as the avian virus H5N9. As the infection by the pH-resistant virus H7N3 could not be abolished after chloroquine administration, these findings demonstrate that CQ inhibits viral replication by pHd dependent mechanisms.

Indeed, CQ is capable of inhibiting infection process, but in previously infected cells the viral replication is unaffected. However, chloroquine may present other mechanisms of antiviral

action that are pH-independent, such as the inhibition of polynucleotidyl transferases like HIV-1 integrase.”

  1. Endosome-mediated viral entry interaction

Chloroquine has been shown to inhibit different viruses requiring a pH-dependent step for entry, such as the Borna disease virus, the minute virus of mice MVMp, and the avian leucosis virus. Of particular interest for human pathology is the report that chloroquine inhibits uncoating of the hepatitis A virus, thus blocking its entire replication cycle.”

  1. Replication of enveloped viruses interaction 

“ Chloroquine also inhibits the replication of members of the Flaviviridae family by affecting the normal proteolytic processing of the flavivirus prM protein to M.16 As a result, viral infectivity is impaired.

Finally, chloroquine induces the production of non-infectious retrovirus particles, as shown with the avian reticuloendotheliosis virus REV-A and with HIV-1.17 The mechanism of inhibition seems to be inhibition of glycosylation of the envelope glycoproteins, as will be discussed below
.”


Further Scientific research:

In-vitro antiviral effects:

Regarding viruses, for reasons probably partly identical involving alkalinisation by chloroquine of the phagolysosome, several studies have shown the effectiveness of this molecule, including against coronaviruses among which is the severe acute respiratory syndrome (SARS)-associated coronavirus.

In 2005, researchers published a study examining the effects of Chloroquine on inhibition of the SARS virus. They found it to have effective antiviral effects on cell cultures, both pre- and post-infection. The mechanisms of action were not fully understood.

Some previous studies had suggested the elevation of pH as a mechanism by which chloroquine reduces the transduction of SARS-CoV pseudotype viruses. In the 2005 study, researchers examined the effect of chloroquine and NH4Cl on the SARS-CoV spike proteins and on its receptor, ACE2:“Immunoprecipitation results of ACE2 clearly demonstrated that effective anti-SARS-CoV concentrations of chloroquine and NH4Cl also impaired the terminal glycosylation of ACE2.”

More recently, a study published in Nature documented the efficacy of both Remdesivir and chloroquine in inhibiting the SARS-CoV-2 virus. In the study, five FDA-approved antiviral drugs were tested for their ability to inhibit the new virus. See their results below:

Our time-of-addition assay demonstrated that Chloroquine functioned at both entry, and at post-entry stages of the 2019-nCoV infection in Vero E6 cells. Besides its antiviral activity, chloroquine has an immune-modulating activity, which may synergistically enhance its antiviral effect in vivo.  

Chloroquine is widely distributed in the whole body, including lung, after oral administration. The EC90 value of chloroquine against the 2019-nCoV in Vero E6 cells was 6.90 μM, which can be clinically achievable as demonstrated in the plasma of rheumatoid arthritis patients who received 500 mg administration.

Chloroquine is a cheap and a safe drug that has been used for more than 70 years and, therefore, it is potentially clinically applicable against the 2019-nCoV.”

These results were confirmed by a later review commissioned by the French government, published in early March 2020.

French researchers analyzed data from 9 studies on cell cultures using Chloroquine, hydroxychloroquine, and chloroquine diphosphate. A number of types of cell cultures were used (including Vero cells and human lung and liver epithelial cells). The studies all indicated an effective antiviral effect against the SARS-CoV-2 virus in vitro.


Clinical Reviews:

There have been several clinical reviews published examining Chloroquine’s antimalarial effects in humans, which are well understood. Below, we present a recent review of its lesser-known effects, on viral and bacterial infections:

A 2007 review paper explored the potential uses of Chloroquine against bacterial, viral, and fungal infections in the 21st century. The researchers analyzed results from numerous studies documenting the effects of the drug on a variety of pathogens.

In vitro data suggests that Chloroquine may have inhibitory effects on at least 15 strains of bacteria, 5 strains of fungi, and 28 viruses (including SARS-CoV, HIV, influenza, yellow fever virus, and HBV).

For viral infections, the authors state the following about Chloroquine (CQ):

The pH increase induced by CQ/HCQ within acidic organelles, including endosomes, lysosomes and Golgi vesicles, is involved in its antiviral activity via two main mechanisms:

  1. First, these drugs might be responsible for inhibition of viruses requiring a pH-dependent step for entry into their host cell.
  2. Second, CQ/HCQ might inhibit post-translational modifications of the virus envelope glycoproteins by proteases and glycosyltransferases within the trans-Golgi network and endoplasmic vesicles.”

An earlier study also explored the various uses of Chloroquine for antiviral effects and highlighted some key studies involving human participants. These included:

  1. Administering 250 mg/day to HIV-1 infected patients above a threshold viral load, in combination with lamivudine and hydroxyurea.
  2. A similar study in Singapore, using 200 mg hydroxychloroquine along with didanosine, and hydroxyurea, daily.

Based on the apparent effects of Chloroquine described above, researchers hypothesized that the antiretroviral effects were attributable to the inhibition of viral particle glycosylation – effectively inhibiting viral replication. Further studies on cell cultures of SARS- and H5N9/A/chicken/Italy/9097/97 avian influenza-infected cells provided more evidence this hypothesis.


Human studies:

Many clinical studies have been published on the effects of Chloroquine for antimalarial effects. These are well-known in the medical and research communities. Below, we highlight two key studies pertaining to the compound’s antiviral effects:

A 2020 study published in the BioScience Trends Journal entitled: “Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in

clinical studies” documented the results of over 100 patients with CoVid-19 who were treated with Chloroquine phosphate.

The results showed that the compound was consistently superior to control in inhibiting the exacerbation of pneumonia, improving lung imaging findings, promoting a virus-negative conversion, and shortening the disease course.

As a result of the findings of this – and other studies - Chloroquine is now recommended

for inclusion in the Guidelines for the Prevention, Diagnosis, and Treatment of Pneumonia Caused by COVID-19 issued by the National Health Commission of the People's Republic of China.


Animal studies:

In a 2008 study, researchers demonstrated that Chloroquine inhibited human coronavirus strains – including the HCoV strain OC43 (HCoV-OC43) – in vitro. They also tested the compound’s effectiveness in inhibiting HCoV-OC43-induced death in newborn mice:

Our results show that a lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with chloroquine acquired transplacentally or via maternal milk. The highest survival rate (98.6%) of the pups was found when mother mice were treated daily with a concentration of 15 mg of chloroquine per kg of body weight. Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg chloroquine and 13% survival when treated with 1 mg/kg chloroquine.”


Toxicology cases:

Since Chloroquine is a widely-used antimalarial agent, its potential adverse effects in humans are well understood. Before prescribing Chloroquine or hydroxychloroquine for malaria treatment or prophylaxis, physicians are typically advised to perform a number of tests in order to prevent adverse effects like retinopathy or kidney issues.

“Chloroquine can cause corneal deposits, posterior subcapsular lens opacity, ciliary body dysfunction, and - most important - irregularity in the macular pigmentation in the early phase, a ring of macular pigment dropout in the advanced stage, and peripheral bone spicule formation, vascular attenuation, and optic disc pallor in the end-stage.

Ocular symptoms of retinopathy include blurred and partial loss of central vision, side vision and in the later stage, night vision.  Symptoms of corneal deposits include haloes and glare.  Clinical research has resulted in precise screening protocols and safe dosing guidelines to prevent ocular toxicity and detect retinal damage at an early stage.

Precaution and Disclaimer:

This Material is Sold For Research Use Only. Terms of Sale Apply. Not for Human Consumption, nor Medical, Veterinary, or Household Uses.


References:

Chloroquine phosphate. (2020). PubChem. US National Library of Medicine. [online]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Chloroquine-phosphate

Chloroquine diphosphate salt. (2020). Sigma Aldrich. Product comparison guide. [online] Available online from https://www.sigmaaldrich.com/catalog/substance/chloroquinediphosphatesalt515865063511?lang=en&region=GB&attrlist=Solubility

Lowe, D. (2020). Covid-19 Small Molecule Therapies Reviewed. Science Translational Medicine. [online] Available from: https://blogs.sciencemag.org/pipeline/archives/2020/03/06/covid-19-small-molecule-therapies-reviewed

Savarino, A., Boelaert, J. R., Cassone, A., Majori, G., & Cauda, R. (2003). Effects of chloroquine on viral infections: an old drug against today’s diseases. The Lancet Infectious Diseases, 3(11), 722–727. doi:10.1016/s1473-3099(03)00806-5 

Lowe, D. (2016). Two Drug Companies Rewrite Some Cancer Biochemistry. Science Translational Medicine. [online] Available from: https://blogs.sciencemag.org/pipeline/archives/2016/02/08/two-drug-companies-rewrite-some-cancer-biochemistry

Chloroquine diphosphate salt. Product Information sheet. Sigma Aldrich. [online[ Available from: https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Product_Information_Sheet/c6628pis.pdf

Lin JW, Spaccapelo R, Schwarzer E, Sajid M, Annoura T, Deroost K, et al. (June 2015). "Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance" (PDF). The Journal of Experimental Medicine. 212 (6): 893–903.

Hempelmann E (March 2007). "Hemozoin biocrystallization in Plasmodium falciparum and the antimalarial activity of crystallization inhibitors". Parasitology Research. 100 (4): 671–6.

Lowe, D. (2016). The Chloroquine Story in Cancer Continues. Science Translational Medicine. [online] Available from: https://blogs.sciencemag.org/pipeline/archives/2016/02/10/the-chloroquine-story-in-cancer-continues

Thomé, R., Lopes, S. C. P., Costa, F. T. M., & Verinaud, L. (2013). Chloroquine: Modes of action of an undervalued drug. Immunology Letters, 153(1-2), 50–57. doi:10.1016/j.imlet.2013.07.004 

Savarino, A., Boelaert, J. R., Cassone, A., Majori, G., & Cauda, R. (2003). Effects of chloroquine on viral infections: an old drug against today’s diseases. The Lancet Infectious Diseases, 3(11), 722–727. doi:10.1016/s1473-3099(03)00806-5 

Keyaerts, E., Vijgen, L., Maes, P., Neyts, J., & Ranst, M. V. (2004). In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochemical and Biophysical Research Communications, 323(1), 264–268. doi:10.1016/j.bbrc.2004.08.085 

Vincent, M. J., Bergeron, E., Benjannet, S., Erickson, B. R., Rollin, P. E., Ksiazek, T. G., … Nichol, S. T. (2005). Virology Journal, 2(1), 69. doi:10.1186/1743-422x-2-69

Manli Wang, Ruiyuan Cao, Leike Zhang, Xinglou Yang, Jia Liu, Mingyue Xu, Zhengli Shi, Zhihong Hu, Wu Zhong, and Gengfu Xiao. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research. doi: 10.1038/s41422-020-0282-0

Colson, P., Rolain, J. M., , Lagier, J.C., Brouqui, P., Raoult, D. (2020). Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. International Journal of Antimicrobial Agents. doi: https://doi.org/10.1016/j.ijantimicag.2020.105932

Rolain, J.-M., Colson, P., & Raoult, D. (2007). Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century. International Journal of Antimicrobial Agents, 30(4), 297–308. doi:10.1016/j.ijantimicag.2007.05.015

Savarino, A., Di Trani, L., Donatelli, I., Cauda, R., & Cassone, A. (2006). New insights into the antiviral effects of chloroquine. The Lancet Infectious Diseases, 6(2), 67–69. doi:10.1016/s1473-3099(06)70361-9 

Gao, J., Tian, Z., & Yang, X. (2020). Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. BioScience Trends. doi:10.5582/bst.2020.01047 

Keyaerts, E., Li, S., Vijgen, L., Rysman, E., Verbeeck, J., Van Ranst, M., & Maes, P. (2009). Antiviral Activity of Chloroquine against Human Coronavirus OC43 Infection in Newborn Mice. Antimicrobial Agents and Chemotherapy, 53(8), 3416–3421. doi:10.1128/aac.01509-08 

Stokkermans, T.J., & Trichonas, G. (2020). Chloroquine And Hydroxychloroquine Toxicity. Treasure Island (FL): StatPearls Publishing. [online]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537086/