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Pathway Description
Chloroquine Action Pathway
Homo sapiens
Drug Action Pathway
Chloroquine is an antimalarial drug used to treat susceptible infections with P. vivax, P. malariae, P. ovale, and P. falciparum. It is also used for second line treatment for rheumatoid arthritis. Chloroquine inhibits the action of heme polymerase, which causes the buildup of toxic heme in Plasmodium species, 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.
References
Chloroquine Pathway References
Ducharme J, Farinotti R: Clinical pharmacokinetics and metabolism of chloroquine. Focus on recent advancements. Clin Pharmacokinet. 1996 Oct;31(4):257-74. doi: 10.2165/00003088-199631040-00003.
Pubmed: 8896943
Coronado LM, Nadovich CT, Spadafora C: Malarial hemozoin: from target to tool. Biochim Biophys Acta. 2014 Jun;1840(6):2032-41. doi: 10.1016/j.bbagen.2014.02.009. Epub 2014 Feb 17.
Pubmed: 24556123
Chou AC, Fitch CD: Heme polymerase: modulation by chloroquine treatment of a rodent malaria. Life Sci. 1992;51(26):2073-8. doi: 10.1016/0024-3205(92)90158-l.
Pubmed: 1474861
Slater AF, Cerami A: Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites. Nature. 1992 Jan 9;355(6356):167-9. doi: 10.1038/355167a0.
Pubmed: 1729651
Vandekerckhove S, D'hooghe M: Quinoline-based antimalarial hybrid compounds. Bioorg Med Chem. 2015 Aug 15;23(16):5098-119. doi: 10.1016/j.bmc.2014.12.018. Epub 2014 Dec 19.
Pubmed: 25593097
FDA Approved Drug Products: Chloroquine Phosphate Oral Tablets: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/083082s050lbl.pdf
FDA: Emergency use Authorization for Hydroxychloroquine and Chloroquine Revoked: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
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