Repositioning Candidate Details
| Candidate ID: | R0214 |
| Source ID: | DB00608 |
| Source Type: | approved; investigational; vet_approved |
| Compound Type: | small molecule |
| Compound Name: | Chloroquine |
| Synonyms: | Chloraquine; Chloroquina; Chloroquinium; N4-(7-chloro-4-quinolinyl)-N1,N1-diethyl-1,4-pentanediamine |
| Molecular Formula: | C18H26ClN3 |
| SMILES: | CCN(CC)CCCC(C)NC1=CC=NC2=CC(Cl)=CC=C12 |
| Structure: |
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| DrugBank Description: | Chloroquine is an aminoquinolone derivative first developed in the 1940s for the treatment of malaria. It was the drug of choice to treat malaria until the development of newer antimalarials such as , , and . Chloroquine and its derivative have since been repurposed for the treatment of a number of other conditions including HIV, systemic lupus erythematosus, and rheumatoid arthritis. **The FDA emergency use authorization for and chloroquine in the treatment of COVID-19 was revoked on 15 June 2020.** Chloroquine was granted FDA Approval on 31 October 1949. |
| CAS Number: | 54-05-7 |
| Molecular Weight: | 319.872 |
| DrugBank Indication: | Chloroquine is indicated to treat infections of _P. vivax_, _P. malariae_, _P. ovale_, and susceptible strains of _P. falciparum_. It is also used to treat extraintestinal amebiasis. Chloroquine is also used off label for the treatment of rheumatic diseases, as well as treatment and prophylaxis of Zika virus. Chloroquine is currently undergoing clinical trials for the treatment of COVID-19. |
| DrugBank Pharmacology: | Chloroquine inhibits the action of heme polymerase, which causes the buildup of toxic heme in _Plasmodium_ species. It has a long duration of action as the half life is 20-60 days. Patients should be counselled regarding the risk of retinopathy with long term usage or high dosage, muscle weakness, and toxicity in children. |
| DrugBank MoA: | Chloroquine inhibits the action of heme polymerase in malarial trophozoites, preventing the conversion of heme to hemazoin. _Plasmodium_ species continue to accumulate toxic heme, killing the parasite. Chloroquine passively diffuses through cell membranes and into endosomes, lysosomes, and Golgi vesicles; where it becomes protonated, trapping the chloroquine in the organelle and raising the surrounding pH. The raised pH in endosomes, prevent virus particles from utilizing their activity for fusion and entry into the cell. Chloroquine does not affect the level of ACE2 expression on cell surfaces, but inhibits terminal glycosylation of ACE2, the receptor that SARS-CoV and SARS-CoV-2 target for cell entry. ACE2 that is not in the glycosylated state may less efficiently interact with the SARS-CoV-2 spike protein, further inhibiting viral entry. |
| Targets: | Glutathione S-transferase A2 inhibitor; Tumor necrosis factor inhibitor; Toll-like receptor 9 inhibitor; Glutathione S-transferase inhibitor; High mobility group protein B1 inhibitor; Glutathione S-transferase Mu 1 inhibitor; Angiotensin-converting enzyme 2 modulator |
| Inclusion Criteria: | Target associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I01 | 552 | Pneumonia | A lung disease that involves lung parenchyma or alveolar inflammation and abnormal alveolar filling with fluid (consolidation and exudation). It results from a variety of causes including infection with bacteria, viruses, fungi or parasites, and chemical or physical injury to the lungs. It is accompanied by fever, chills, cough, and difficulty in breathing. http://en.wikipedia.org/wiki/Pneumonia | disease of anatomical entity/respiratory system disease/ lower respiratory tract disease/lung disease | Details |
| I15 | 1290 | Bone disease | A connective tissue disease that affects the structure or development of bone or causes an impairment of normal bone function. http://en.wikipedia.org/wiki/Bone_disease | disease of anatomical entity/ musculoskeletal system disease/connective tissue disease | Details |