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Showing metabocard for Chloroquine (HMDB0014746)
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| Version | 4.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status | Expected but not Quantified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Creation Date | 2012-09-06 15:16:50 UTC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Update Date | 2020-02-26 21:40:16 UTC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HMDB ID | HMDB0014746 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary Accession Numbers |
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| Metabolite Identification | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Common Name | Chloroquine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | Chloroquine is only found in individuals that have used or taken this drug. It is a 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]The mechanism of plasmodicidal action of chloroquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit heme polymerase activity. This results in accumulation of free heme, which is toxic to the parasites. nside red blood cells, the malarial parasite must degrade hemoglobin to acquire essential amino acids, which the parasite requires to construct its own protein and for energy metabolism. Digestion is carried out in a vacuole of the parasite cell.During this process, the parasite produces the toxic and soluble molecule heme. The heme moiety consists of a porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin, a non-toxic molecule. Hemozoin collects in the digestive vacuole as insoluble crystals.Chloroquine enters the red blood cell, inhabiting parasite cell, and digestive vacuole by simple diffusion. Chloroquine then becomes protonated (to CQ2+), as the digestive vacuole is known to be acidic (pH 4.7); chloroquine then cannot leave by diffusion. Chloroquine caps hemozoin molecules to prevent further biocrystallization of heme, thus leading to heme buildup. Chloroquine binds to heme (or FP) to form what is known as the FP-Chloroquine complex; this complex is highly toxic to the cell and disrupts membrane function. Action of the toxic FP-Chloroquine and FP results in cell lysis and ultimately parasite cell autodigestion. In essence, the parasite cell drowns in its own metabolic products. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structure | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Synonyms |
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| Chemical Formula | C18H26ClN3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Average Molecular Weight | 319.872 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Monoisotopic Molecular Weight | 319.181525554 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| IUPAC Name | 7-chloro-N-[5-(diethylamino)pentan-2-yl]quinolin-4-amine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Traditional Name | 7-chloro-N-[5-(diethylamino)pentan-2-yl]quinolin-4-amine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAS Registry Number | 54-05-7 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| SMILES | CCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Identifier | InChI=1S/C18H26ClN3/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) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Key | WHTVZRBIWZFKQO-UHFFFAOYSA-N | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Chemical Taxonomy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | belongs to the class of organic compounds known as 4-aminoquinolines. These are organic compounds containing an amino group attached to the 4-position of a quinoline ring system. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Super Class | Organoheterocyclic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Class | Quinolines and derivatives | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sub Class | Aminoquinolines and derivatives | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Direct Parent | 4-aminoquinolines | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative Parents | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Substituents |
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| Molecular Framework | Aromatic heteropolycyclic compounds | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External Descriptors |
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| Ontology | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Disposition | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Physical Properties | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| State | Solid | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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| Spectra | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Biological Properties | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cellular Locations |
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| Biospecimen Locations |
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| Tissue Locations | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pathways |
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| Normal Concentrations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Abnormal Concentrations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Predicted Concentrations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Associated Disorders and Diseases | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Disease References | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Associated OMIM IDs | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External Links | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DrugBank ID | DB00608 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Phenol Explorer Compound ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| FoodDB ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| KNApSAcK ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Chemspider ID | 2618 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| KEGG Compound ID | C07625 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BioCyc ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BiGG ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikipedia Link | Chloroquine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| METLIN ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PubChem Compound | 2719 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PDB ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ChEBI ID | 3638 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Food Biomarker Ontology | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| VMH ID | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| References | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Material Safety Data Sheet (MSDS) | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| General References | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Enzymes
- General function:
- Involved in glutathione transferase activity
- Specific function:
- Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
- Gene Name:
- GSTA2
- Uniprot ID:
- P09210
- Molecular weight:
- 25663.675
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
- Gene Name:
- CYP3A4
- Uniprot ID:
- P08684
- Molecular weight:
- 57255.585
References
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
- Gene Name:
- CYP2D6
- Uniprot ID:
- P10635
- Molecular weight:
- 55768.94
References
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
- Gene Name:
- CYP3A5
- Uniprot ID:
- P20815
- Molecular weight:
- 57108.065
References
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
- Gene Name:
- CYP1A1
- Uniprot ID:
- P04798
- Molecular weight:
- 58164.815
References
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
- General function:
- Involved in monooxygenase activity
- Specific function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
- Gene Name:
- CYP2C8
- Uniprot ID:
- P10632
- Molecular weight:
- 55824.275
References
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
- General function:
- Involved in tumor necrosis factor receptor binding
- Specific function:
- Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation
- Gene Name:
- TNF
- Uniprot ID:
- P01375
- Molecular weight:
- 25644.1
References
- Jang CH, Choi JH, Byun MS, Jue DM: Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes. Rheumatology (Oxford). 2006 Jun;45(6):703-10. Epub 2006 Jan 17. [PubMed:16418198 ]
- Rachmilewitz D, Karmeli F, Shteingart S, Lee J, Takabayashi K, Raz E: Immunostimulatory oligonucleotides inhibit colonic proinflammatory cytokine production in ulcerative colitis. Inflamm Bowel Dis. 2006 May;12(5):339-45. [PubMed:16670522 ]
- Wozniacka A, Lesiak A, Narbutt J, McCauliffe DP, Sysa-Jedrzejowska A: Chloroquine treatment influences proinflammatory cytokine levels in systemic lupus erythematosus patients. Lupus. 2006;15(5):268-75. [PubMed:16761500 ]
- Lim EJ, Lee SH, Lee JG, Chin BR, Bae YS, Kim JR, Lee CH, Baek SH: Activation of toll-like receptor-9 induces matrix metalloproteinase-9 expression through Akt and tumor necrosis factor-alpha signaling. FEBS Lett. 2006 Aug 7;580(18):4533-8. Epub 2006 Jul 17. [PubMed:16870179 ]
- Dias-Melicio LA, Calvi SA, Bordon AP, Golim MA, Peracoli MT, Soares AM: Chloroquine is therapeutic in murine experimental model of paracoccidioidomycosis. FEMS Immunol Med Microbiol. 2007 Jun;50(1):133-43. Epub 2007 Apr 23. [PubMed:17456179 ]
- General function:
- Involved in protein binding
- Specific function:
- Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific of microorganisms. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response
- Gene Name:
- TLR9
- Uniprot ID:
- Q9NR96
- Molecular weight:
- 115858.7
References
- Trevani AS, Chorny A, Salamone G, Vermeulen M, Gamberale R, Schettini J, Raiden S, Geffner J: Bacterial DNA activates human neutrophils by a CpG-independent pathway. Eur J Immunol. 2003 Nov;33(11):3164-74. [PubMed:14579285 ]
- Rutz M, Metzger J, Gellert T, Luppa P, Lipford GB, Wagner H, Bauer S: Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. Eur J Immunol. 2004 Sep;34(9):2541-50. [PubMed:15307186 ]
- Lenert P: Inhibitory oligodeoxynucleotides - therapeutic promise for systemic autoimmune diseases? Clin Exp Immunol. 2005 Apr;140(1):1-10. [PubMed:15762869 ]
- Huang LY, Ishii KJ, Akira S, Aliberti J, Golding B: Th1-like cytokine induction by heat-killed Brucella abortus is dependent on triggering of TLR9. J Immunol. 2005 Sep 15;175(6):3964-70. [PubMed:16148144 ]
- Merrell MA, Ilvesaro JM, Lehtonen N, Sorsa T, Gehrs B, Rosenthal E, Chen D, Shackley B, Harris KW, Selander KS: Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity. Mol Cancer Res. 2006 Jul;4(7):437-47. [PubMed:16849519 ]
Transporters
- General function:
- Involved in ATP binding
- Specific function:
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
- Gene Name:
- ABCB1
- Uniprot ID:
- P08183
- Molecular weight:
- 141477.3
References
- Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674 ]