Investigational Drug Details
| Drug ID: | D243 |
| Drug Name: | Nitazoxanide |
| Synonyms: | Nitazoxanide |
| Type: | Chemical drug |
| DrugBank ID: | DB00507 |
| DrugBank Description: | Nitazoxanide belongs to the class of drugs known as _thiazolides_. Nitazoxanide (NTZ) is a broad-spectrum anti-infective drug that markedly modulates the survival, growth, and proliferation of a range of extracellular and intracellular protozoa, helminths, anaerobic and microaerophilic bacteria, in addition to viruses. This drug is effective in the treatment of gastrointestinal infections including Cryptosporidium parvum or Giardia lamblia in healthy subjects. It is generally well tolerated. Nitazoxanide is a first-line, standard treatment for illness caused by C. parvum or G. lamblia infection in healthy (not immunosuppressed) adults and children and may also be considered in the treatment of illnesses caused by other protozoa or helminths . Recently, this drug has been studied as a broad-spectrum antiviral agent due to its ability to inhibit the replication of several RNA and DNA viruses . |
| PubChem ID: | 41684 |
| CasNo: | 55981-09-4 |
| Repositioning for NAFLD: | Yes |
| SMILES: | C(=O)(Nc1sc(cn1)N(=O)=O)c1c(OC(=O)C)cccc1 |
| Structure: |
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| InChiKey: | YQNQNVDNTFHQSW-UHFFFAOYSA-N |
| Molecular Weight: | 307.287 |
| DrugBank Targets: | Pyruvate-flavodoxin oxidoreductase antagonist&inhibitor |
| DrugBank MoA: | The most widely accepted mechanism of NTZ is believed to be the disruption of the energy metabolism in anaerobic microbes by inhibition of the pyruvate: ferredoxin/flavodoxin oxidoreductase (PFOR) cycle . In parasitic-protozoa, Nitazoxanide also induces lesions in the cell membranes and depolarizes the mitochondrial membrane while inhibiting quinone oxidoreductase NQO1, nitroreductase-1 and protein disulphide isomerase enzymes. In addition, this drug also inhibits the glutathione-S-transferase (a major detoxifying enzyme) and modulates the Avr-14 gene, encoding for the alpha-type subunit of glutamate-gated chloride ion channel present in nematodes. Aside from its well understood non-competitive inhibition of the PFOR in anaerobic bacteria, NTZ also demonstrates various other antibacterial mechanisms. It inhibits pyruvate dehydrogenase in E Coli, disrupts the membrane potential and pH homeostasis in the Mycobacterium tuberculosis, suppresses the chaperone/usher (CU) pathway of the gram-negative bacteria, and stimulates host macrophage autophagy in tuberculosis patients . NTZ also suppresses viral replication by inhibiting the maturation of the viral hemagglutinin and the viral transcription factor immediate early 2 (IE2) as well as by activating the eukaryotic translation initiation factor 2α (an antiviral intracellular protein). Lastly, NTZ exhibits an inhibitory effect on tumor cell progression by altering drug detoxification (glutathione-S-transferase P1), unfolded protein response, autophagy, anti-cytokines activity, and c-Myc inhibition . |
| DrugBank Pharmacology: | The general effect of this medication is the prevention of microbe activity through disruption of important energy pathways for survival and proliferation . Nitazoxanide exhibits antiprotozoal activity by interfering with the pyruvate ferredoxin/flavodoxin oxidoreductase dependent electron transfer reaction, an essential reaction need for anaerobic energy metabolism of various microorganisms. Sporozoites of Cryptosporidium parvum and trophozoites of Giardia lamblia are therefore inhibited, relieving symptoms of diahrrea . Interference with the PFOR enzyme-dependent electron transfer reaction may only be one of the many pathways by which nitazoxanide exhibits antiprotozoal activity . |
| DrugBank Indication: | For the treatment of diarrhea in adults and children caused by the protozoa <i>Giardia lamblia</i>, and for the treatment of diarrhea in children caused by the protozoan, <i>Cryptosporidium parvum</i> . Nitazoxanide has not been shown to be superior to placebo medication for the management of diarrhea caused by Cryptosporidium parvum in patients with HIV/immunodeficiency . |
| Targets: | POR inhibitor |
| Therapeutic Category: | Antiprotozoal drug |
| Clinical Trial Progress: | Phase 2 completed (NCT03656068) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0353 | NCT03656068 | Phase 2 | Completed | No Results Available | December 15, 2018 | December 29, 2021 | Details |
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