Repositioning Candidate Details
| Candidate ID: | R0544 |
| Source ID: | DB01611 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Hydroxychloroquine |
| Synonyms: | (±)-hydroxychloroquine; 2-((4-((7-chloro-4-quinolyl)amino)pentyl)ethylamino)ethanol; 2-(N-(4-(7-chlor-4-chinolylamino)-4-methylbutyl)ethylamino)ethanol; 7-chloro-4-(4-(ethyl(2-hydroxyethyl)amino)-1-methylbutylamino)quinoline; 7-chloro-4-(4-(N-ethyl-N-β-hydroxyethylamino)-1-methylbutylamino)quinoline; 7-chloro-4-[4-(N-ethyl-N-β-hydroxyethylamino)-1-methylbutylamino]quinoline; 7-chloro-4-[5-(N-ethyl-N-2-hydroxyethylamino)-2-pentyl]aminoquinoline; Oxichlorochine; Oxichloroquine |
| Molecular Formula: | C18H26ClN3O |
| SMILES: | CCN(CCO)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1 |
| Structure: |
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| DrugBank Description: | Hydroxychloroquine is a racemic mixture consisting of an R and S enantiomer. Hydroxychloroquine is an aminoquinoline like . It is a commonly prescribed medication in the treatment of uncomplicated malaria, rheumatoid arthritis, chronic discoid lupus erythematosus, and systemic lupus erythematosus. Hydroxychloroquine is also used for the prophylaxis of malaria in regions where chloroquine resistance is unlikely. It was developed during World War II as a derivative of with less severe side effects. Chloroquine and hydroxychloroquine are both being investigated for the treatment of SARS-CoV-2. **The FDA emergency use authorization for hydroxychloroquine and in the treatment of COVID-19 was revoked on 15 June 2020.** Hydroxychloroquine was granted FDA approval on 18 April 1955. A recent study reported a fatality in the group being treated with hydroxychloroquine for COVID-19. |
| CAS Number: | 118-42-3 |
| Molecular Weight: | 335.872 |
| DrugBank Indication: | Hydroxychloroquine is indicated for the prophylaxis of malaria where chloroquine resistance is not reported, treatment of uncomplicated malaria (caused by _P. falciparum_, _P. malariae_, _P. ovale_, or _P. vivax_), chronic discoid lupus erythematosus, systemic lupus erythematosus, acute rheumatoid arthritis, and chronic rheumatoid arthritis. |
| DrugBank Pharmacology: | Hydroxychloroquine affects the function of lysozomes in humans as well as plasmodia. Altering the pH of the lysozomes reduces low affinity self antigen presentation in autoimmue diseases and interferes with the ability of plasmodia to proteolyse hemoglobin for their energy requirements. Hydroxychloroquine has a long duration of action as it may be taken on a weekly basis for some indications. Hydroxychloroquine may lead to severe hypoglycemia and so diabetic patients are advised to monitor their blood glucose levels. Hydroxychloroquine is not effective against malaria in areas where chloroquine resistance has been reported. |
| DrugBank MoA: | The exact mechanisms of hydroxychloroquine are unknown. It has been shown that hydroxychloroquine accumulates in the lysosomes of the malaria parasite, raising the pH of the vacuole. This activity interferes with the parasite's ability to proteolyse hemoglobin, preventing the normal growth and replication of the parasite. Hydroxychloroquine can also interfere with the action of parasitic heme polymerase, allowing for the accumulation of the toxic product beta-hematin. Hydroxychloroquine accumulation in human organelles also raise their pH, which inhibits antigen processing, prevents the alpha and beta chains of the major histocompatibility complex (MHC) class II from dimerizing, inhibits antigen presentation of the cell, and reduces the inflammatory response. Elevated pH in the vesicles may alter the recycling of MHC complexes so that only the high affinity complexes are presented on the cell surface. Self peptides bind to MHC complexes with low affinity and so they will be less likely to be presented to autoimmune T cells. Hydroxychloroquine also reduces the release of cytokines like interleukin-1 and tumor necrosis factor, possibly through inhibition of Toll-like receptors. The raised pH in endosomes, prevent virus particles (such as SARS-CoV and SARS-CoV-2) from utilizing their activity for fusion and entry into the cell. Hydroxychloroquine 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: | DNA cross-linking/alkylation; Toll-like receptor 7 antagonist; Toll-like receptor 9 antagonist; Angiotensin-converting enzyme 2 modulator |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| 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 |