Investigational Drug Details
| Drug ID: | D173 |
| Drug Name: | Chloroquine |
| Synonyms: | |
| Type: | small molecule |
| DrugBank ID: | DB00608 |
| DrugBank Description: | The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. |
| PubChem ID: | 2719 |
| CasNo: | 54-05-7 |
| Repositioning for NAFLD: | Yes |
| SMILES: | CCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1 |
| Structure: |
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| InChiKey: | WHTVZRBIWZFKQO-UHFFFAOYSA-N |
| Molecular Weight: | 319.872 |
| DrugBank Targets: | Glutathione S-transferase A2; Tumor necrosis factor; Toll-like receptor 9; Glutathione S-transferase; High mobility group protein B1; Glutathione S-transferase Mu 1; Angiotensin-converting enzyme 2 |
| DrugBank MoA: | The mechanism behind the plasmodicidal action of chloroquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit the heme polymerase activity, resulting in an accumulation of free heme, which is toxic to the parasites. Inside red blood cells, the malarial parasite must degrade hemoglobin in vacuoles to acquire essential amino acids, which the parasite requires to construct its own protein and for energy metabolism. Degradation of hemoglobin involves the production of toxic heme, which consists of a porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemosoin, which is non-toxic, which is collected in the digestive vacuole as insoluble crystals. Chloroquine enters the red blood cell, inhabiting parasite cell, and digestive vacuole by simple diffusion. Upon entry into the digestive vacuole, chloroquine become protonated due the acidic nature of the vacuole and this prevents chloroquine from leaving the vacuole via simple diffusion. The drug then mediates its plasmodicidal effect by capping hemozoin molecules to prevent further biocrystallization of heme, leading to heme buildup. Chloroquine can also bind to heme to form the toxic FP-Chloroquine complex, which is highly toxic to the cell. The complex disrupts the membrane function to promote cell lysis and ultimately, parasitic cell autodigestion. |
| DrugBank Pharmacology: | Chloroquine is the prototype anti malarial drug, most widely used to treat all types of malaria except for disease caused by chloroquine resistant <i>Plasmodium falciparum</i>. It is highly effective against erythrocytic forms of <i>Plasmodium vivax</i>, <i>Plasmodium ovale</i> and <i>Plasmodium malariae</i>, sensitive strains of <i>Plasmodium falciparum</i> and gametocytes of <i>Plasmodium vivax</i>. Being alkaline, the drug reaches high concentration within the food vacuoles of the parasite and raises its pH. It is found to induce rapid clumping of the pigment. Chloroquine inhibits the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin, thereby resulting in the accumulation of toxic heme within the parasite. It may also interfere with the biosynthesis of nucleic acids. |
| DrugBank Indication: | For the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum, Second-line agent in treatment of Rheumatoid Arthritis |
| Targets: | |
| Therapeutic Category: | |
| Clinical Trial Progress: | |
| Latest Progress: |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L1990 | NCT03081676 | COMPLETED | NO | 2017-03-08 | 2019-06-27 | Details | |
| L2912 | NCT05689372 | NOT_YET_RECRUITING | NO | 2025-03-31 | 2024-09-19 | Details | |
| L2942 | NCT02048189 | PHASE4 | TERMINATED | NO | 2012-03-08 | 2024-02-21 | Details |
| L4685 | NCT00654121 | PHASE2 | COMPLETED | NO | 2000-02 | 2008-04-07 | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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