Component
Albendazole
Albendazole. Species, exposure and limitations are retained in each linked claim.
4 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
How nutrients reach it in more than one step
Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
Where it participates (unsigned role)
The relative potencies of the benzimidazole analogs in rat embryo micromass culture, nocodazole greater than mebendazole approximately equal to albendazole much greater than thiabendazole, mirrored their effectiveness in an assay for in vitro inhibition of mammalian tubulin polymerization, immunofluorescent staining with a monoclonal antibody to beta-tubulin revealed that these agents elicited mitotic arrest, and with the exception of thiabendazole these agents should be considered potential developmental toxicants since they inhibit cell growth and differentiation at nanomolar concentrations.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/mebendazole-research/1553749.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4c8ca680cbc4ebd8441d3d8c083a98587c81141280e9fa61388751264f1ea2ac", "start_char": 0, "end_char": 1384, "text_sha256": "4c8ca680cbc4ebd8441d3d8c083a98587c81141280e9fa61388751264f1ea2ac"}
- experimental_model
- Rat embryo midbrain and limb bud micromass cultures assessed for differentiation and cytotoxicity
- exposure
- Mebendazole, thiabendazole, nocodazole and colchicine, compared with albendazole
- limitations
- An in vitro developmental toxicity screen. It links the effect to the mammalian tubulin binding directly, by showing the potency order matches; it is not a pregnancy outcome.
- nutrient_topic
- Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. · Mebendazole
- organism
- Rat
- plain_language
- The very property that makes it a cancer drug candidate is the property that makes it a suspected developmental toxin.
- primary_references
- [mbz-p1553749] Effects of benzimidazole analogs on cultures of differentiating rodent embryonic cells. (1992). https://pubmed.ncbi.nlm.nih.gov/1553749/ DOI: 10.1016/0041-008x(92)90019-o
- tissue_or_cell_type
- Embryonic midbrain and limb bud cells
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat embryo midbrain and limb bud micromass cultures assessed for differentiation and cytotoxicity · source_derived_draft · unverified_draft
### mbz-developmental-toxicity-is-the-same-target The relative potencies of the benzimidazole analogs in rat embryo micromass culture, nocodazole greater than mebendazole approximately equal to albendazole much greater than thiabendazole, mirrored their effectiveness in an assay for in vitro inhibition of mammalian tubulin polymerization, immunofluorescent staining with a monoclonal antibody to beta-tubulin revealed that these agents elicited mitotic arrest, and with the exception of thiabendazole these agents should be considered potential developmental toxicants since they inhibit cell growth and differentiation at nanomolar concentrations. Condition category: normal nutrient_topic: Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. plain_language: The very property that makes it a cancer drug candidate is the property that makes it a suspected developmental toxin. organism: Rat tissue_or_cell_type: Embryonic midbrain and limb bud cells experimental_model: Rat embryo midbrain and limb bud micromass cultures assessed for differentiation and cytotoxicity limitations: An in vitro developmental toxicity screen. It links the effect to the mammalian tubulin binding directly, by showing the potency order matches; it is not a pregnancy outcome. exposure: Mebendazole, thiabendazole, nocodazole and colchicine, compared with albendazole evidence_span: {"source_cache": "artifacts/mebendazole-research/1553749.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4c8ca680cbc4ebd8441d3d8c083a98587c81141280e9fa61388751264f1ea2ac", "start_char": 0, "end_char": 1384, "text_sha256": "4c8ca680cbc4ebd8441d3d8c083a98587c81141280e9fa61388751264f1ea2ac"} [mbz-p1553749] Effects of benzimidazole analogs on cultures of differentiating rodent embryonic cells. (1992). https://pubmed.ncbi.nlm.nih.gov/1553749/ DOI: 10.1016/0041-008x(92)90019-o
Complete structured claim and evidenceOf four benzimidazole anthelmintics tested on purified cytoplasmic and mitochondrial malate dehydrogenase from Ascaris suum, Fasciola hepatica and Moniezia expansa, mebendazole exhibited the highest percentage inhibitions, and the authors conclude that cytoplasmic and mitochondrial malate dehydrogenase regulating glycogen synthesis are the sites of mebendazole inhibitory activity while the sites for the other anthelmintics remain unclear.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/mebendazole-research/3617430.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "addd86672cc2c829b72354c05387892908f94c49f81e1236e372432c68a622fe", "start_char": 0, "end_char": 589, "text_sha256": "addd86672cc2c829b72354c05387892908f94c49f81e1236e372432c68a622fe"}
- experimental_model
- Inhibition assays on purified cytoplasmic and mitochondrial malate dehydrogenase from three helminths
- exposure
- Albendazole, parbendazole, mebendazole and thiabendazole on purified enzyme extracts
- limitations
- A competing target claim. Enzyme inhibition percentages in purified extracts do not establish that this happens at therapeutic concentrations in a living parasite.
- nutrient_topic
- Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. · Mebendazole
- organism
- Helminth
- plain_language
- A rival account: the drug jams an enzyme of the worm’s sugar metabolism, and mebendazole does it hardest.
- primary_references
- [mbz-p3617430] Inhibition of malate dehydrogenase enzymes by benzimidazole anthelmintics. (1987). https://pubmed.ncbi.nlm.nih.gov/3617430/ DOI: 10.1016/0304-4017(87)90048-3
- tissue_or_cell_type
- Ascaris suum, Fasciola hepatica and Moniezia expansa
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inhibition assays on purified cytoplasmic and mitochondrial malate dehydrogenase from three helminths · source_derived_draft · unverified_draft
### mbz-inhibits-malate-dehydrogenase Of four benzimidazole anthelmintics tested on purified cytoplasmic and mitochondrial malate dehydrogenase from Ascaris suum, Fasciola hepatica and Moniezia expansa, mebendazole exhibited the highest percentage inhibitions, and the authors conclude that cytoplasmic and mitochondrial malate dehydrogenase regulating glycogen synthesis are the sites of mebendazole inhibitory activity while the sites for the other anthelmintics remain unclear. Condition category: normal nutrient_topic: Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. plain_language: A rival account: the drug jams an enzyme of the worm’s sugar metabolism, and mebendazole does it hardest. organism: Helminth tissue_or_cell_type: Ascaris suum, Fasciola hepatica and Moniezia expansa experimental_model: Inhibition assays on purified cytoplasmic and mitochondrial malate dehydrogenase from three helminths limitations: A competing target claim. Enzyme inhibition percentages in purified extracts do not establish that this happens at therapeutic concentrations in a living parasite. exposure: Albendazole, parbendazole, mebendazole and thiabendazole on purified enzyme extracts evidence_span: {"source_cache": "artifacts/mebendazole-research/3617430.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "addd86672cc2c829b72354c05387892908f94c49f81e1236e372432c68a622fe", "start_char": 0, "end_char": 589, "text_sha256": "addd86672cc2c829b72354c05387892908f94c49f81e1236e372432c68a622fe"} [mbz-p3617430] Inhibition of malate dehydrogenase enzymes by benzimidazole anthelmintics. (1987). https://pubmed.ncbi.nlm.nih.gov/3617430/ DOI: 10.1016/0304-4017(87)90048-3
Complete structured claim and evidencePyruvate kinase and phosphoenolpyruvate carboxykinase activities in the Echinococcus granulosus cyst wall were markedly inhibited by mebendazole and albendazole while fumarate hydratase activity showed no apparent change, with inhibition rates in the mebendazole group of 85 to 88% and 90 to 92% respectively against 55.3% and 71.6% in the albendazole group, suggesting that these two enzymes may be an important site attacked by effective anti-hydatid drugs.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/mebendazole-research/8010090.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "581715173f3b7176eda8a357166f1647196f646769b75ee7ca9070342a9c312b", "start_char": 0, "end_char": 933, "text_sha256": "581715173f3b7176eda8a357166f1647196f646769b75ee7ca9070342a9c312b"}
- experimental_model
- Enzyme activity assays on Echinococcus granulosus cyst wall from infected mice after 7 to 14 days of treatment
- exposure
- Mebendazole 25 to 50, albendazole 300 and praziquantel 500 milligrams per kilogram daily by gavage
- limitations
- An in vivo enzyme measurement with a head-to-head dose comparison, though the doses are not equipotent and the cyst wall is one tissue.
- nutrient_topic
- Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. · Mebendazole
- organism
- Cestode
- plain_language
- In a live infection mebendazole shut down two sugar-handling enzymes almost completely, and did so harder than albendazole.
- primary_references
- [mbz-p8010090] Effects of mebendazole, albendazole, and praziquantel on fumarate hydratase, pyruvate kinase, and phosphoenolpyruvate carboxykinase of Echinococcus granulosus cyst wall harbored in mice. (1994). https://pubmed.ncbi.nlm.nih.gov/8010090/
- tissue_or_cell_type
- Hydatid cyst wall
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme activity assays on Echinococcus granulosus cyst wall from infected mice after 7 to 14 days of treatment · source_derived_draft · unverified_draft
### mbz-inhibits-pk-and-pepck Pyruvate kinase and phosphoenolpyruvate carboxykinase activities in the Echinococcus granulosus cyst wall were markedly inhibited by mebendazole and albendazole while fumarate hydratase activity showed no apparent change, with inhibition rates in the mebendazole group of 85 to 88% and 90 to 92% respectively against 55.3% and 71.6% in the albendazole group, suggesting that these two enzymes may be an important site attacked by effective anti-hydatid drugs. Condition category: normal nutrient_topic: Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. plain_language: In a live infection mebendazole shut down two sugar-handling enzymes almost completely, and did so harder than albendazole. organism: Cestode tissue_or_cell_type: Hydatid cyst wall experimental_model: Enzyme activity assays on Echinococcus granulosus cyst wall from infected mice after 7 to 14 days of treatment limitations: An in vivo enzyme measurement with a head-to-head dose comparison, though the doses are not equipotent and the cyst wall is one tissue. exposure: Mebendazole 25 to 50, albendazole 300 and praziquantel 500 milligrams per kilogram daily by gavage evidence_span: {"source_cache": "artifacts/mebendazole-research/8010090.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "581715173f3b7176eda8a357166f1647196f646769b75ee7ca9070342a9c312b", "start_char": 0, "end_char": 933, "text_sha256": "581715173f3b7176eda8a357166f1647196f646769b75ee7ca9070342a9c312b"} [mbz-p8010090] Effects of mebendazole, albendazole, and praziquantel on fumarate hydratase, pyruvate kinase, and phosphoenolpyruvate carboxykinase of Echinococcus granulosus cyst wall harbored in mice. (1994). https://pubmed.ncbi.nlm.nih.gov/8010090/
Complete structured claim and evidenceAlbendazole-resistant Giardia lines showed major chromosome rearrangements and differences in the cytoskeleton, particularly the median body, implicating the cytoskeleton in the mechanism of resistance, but sequence data spanning the region encoding phenylalanine at position 200 demonstrated that the beta-tubulin gene did not carry a mutation at that codon, suggesting that phenylalanine at position 200 is not necessary for benzimidazole resistance.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/mebendazole-research/9158790.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1e25da8738886a9f416bb8411755eca925e232495786f938ef8f9afac40de30", "start_char": 0, "end_char": 1295, "text_sha256": "b1e25da8738886a9f416bb8411755eca925e232495786f938ef8f9afac40de30"}
- experimental_model
- Albendazole resistance induced in three Giardia cultures by stepwise drug exposure, with beta-tubulin sequencing
- exposure
- Growth in successively increasing albendazole, with immunofluorescence and PCR across codon 200
- limitations
- A counterexample obtained with albendazole rather than mebendazole, in a protozoan rather than a nematode. It is recorded because it tests the codon-200 rule directly and the rule fails.
- nutrient_topic
- Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. · Mebendazole
- organism
- Giardia
- plain_language
- Resistant parasites that never touched the famous mutation, so it cannot be the only route.
- primary_references
- [mbz-p9158790] Albendazole resistance in Giardia is correlated with cytoskeletal changes but not with a mutation at amino acid 200 in beta-tubulin. (1996). https://pubmed.ncbi.nlm.nih.gov/9158790/ DOI: 10.1089/mdr.1996.2.303
- tissue_or_cell_type
- Cytoskeleton and beta-tubulin gene
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Albendazole resistance induced in three Giardia cultures by stepwise drug exposure, with beta-tubulin sequencing · source_derived_draft · unverified_draft
### mbz-resistance-without-codon-200 Albendazole-resistant Giardia lines showed major chromosome rearrangements and differences in the cytoskeleton, particularly the median body, implicating the cytoskeleton in the mechanism of resistance, but sequence data spanning the region encoding phenylalanine at position 200 demonstrated that the beta-tubulin gene did not carry a mutation at that codon, suggesting that phenylalanine at position 200 is not necessary for benzimidazole resistance. Condition category: normal nutrient_topic: Mebendazole research collection; topical membership is not evidence of a direct clinical effect, and mebendazole is recorded separately from albendazole, from the benzimidazole class and from its own crystal forms. plain_language: Resistant parasites that never touched the famous mutation, so it cannot be the only route. organism: Giardia tissue_or_cell_type: Cytoskeleton and beta-tubulin gene experimental_model: Albendazole resistance induced in three Giardia cultures by stepwise drug exposure, with beta-tubulin sequencing limitations: A counterexample obtained with albendazole rather than mebendazole, in a protozoan rather than a nematode. It is recorded because it tests the codon-200 rule directly and the rule fails. exposure: Growth in successively increasing albendazole, with immunofluorescence and PCR across codon 200 evidence_span: {"source_cache": "artifacts/mebendazole-research/9158790.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1e25da8738886a9f416bb8411755eca925e232495786f938ef8f9afac40de30", "start_char": 0, "end_char": 1295, "text_sha256": "b1e25da8738886a9f416bb8411755eca925e232495786f938ef8f9afac40de30"} [mbz-p9158790] Albendazole resistance in Giardia is correlated with cytoskeletal changes but not with a mutation at amino acid 200 in beta-tubulin. (1996). https://pubmed.ncbi.nlm.nih.gov/9158790/ DOI: 10.1089/mdr.1996.2.303
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.