Component
The colchicine binding site on tubulin
The colchicine binding site on tubulin. Species, exposure and limitations are retained in each linked claim.
3 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.
What acts on it
Inhibition of colchicine binding to Ascaris suum embryonic tubulin by mebendazole and fenbendazole appeared to be noncompetitive, whereas the same compounds appeared to be competitive inhibitors of colchicine binding to bovine brain tubulin.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/mebendazole-research/7388055.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5613d7fb281b4fd39b17bfdbafaf0ea823fb63b928048a9dd112fb71bf4cd2b7", "start_char": 0, "end_char": 1209, "text_sha256": "5613d7fb281b4fd39b17bfdbafaf0ea823fb63b928048a9dd112fb71bf4cd2b7"}
- experimental_model
- Inhibition of tritiated colchicine binding to cytosolic tubulin from 8-day Ascaris suum embryos and from bovine brain
- exposure
- Mebendazole and fenbendazole compared on the two tubulins in the same assay
- limitations
- The founding selectivity result. It measures embryonic tubulin; the study in this collection that measured intestinal tubulin found a far smaller difference.
- 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
- Nematode and cattle
- plain_language
- It does not even bind the two tubulins the same way: it competes with colchicine on ours and not on the worm’s.
- primary_references
- [mbz-p7388055] Interaction of anthelmintic benzimidazoles with Ascaris suum embryonic tubulin. (1980). https://pubmed.ncbi.nlm.nih.gov/7388055/ DOI: 10.1016/0304-4165(80)90431-6
- tissue_or_cell_type
- Embryonic nematode tubulin and bovine brain tubulin
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inhibition of tritiated colchicine binding to cytosolic tubulin from 8-day Ascaris suum embryos and from bovine brain · source_derived_draft · unverified_draft
### mbz-binding-mode-differs Inhibition of colchicine binding to Ascaris suum embryonic tubulin by mebendazole and fenbendazole appeared to be noncompetitive, whereas the same compounds appeared to be competitive inhibitors of colchicine binding to bovine brain tubulin. 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: It does not even bind the two tubulins the same way: it competes with colchicine on ours and not on the worm’s. organism: Nematode and cattle tissue_or_cell_type: Embryonic nematode tubulin and bovine brain tubulin experimental_model: Inhibition of tritiated colchicine binding to cytosolic tubulin from 8-day Ascaris suum embryos and from bovine brain limitations: The founding selectivity result. It measures embryonic tubulin; the study in this collection that measured intestinal tubulin found a far smaller difference. exposure: Mebendazole and fenbendazole compared on the two tubulins in the same assay evidence_span: {"source_cache": "artifacts/mebendazole-research/7388055.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5613d7fb281b4fd39b17bfdbafaf0ea823fb63b928048a9dd112fb71bf4cd2b7", "start_char": 0, "end_char": 1209, "text_sha256": "5613d7fb281b4fd39b17bfdbafaf0ea823fb63b928048a9dd112fb71bf4cd2b7"} [mbz-p7388055] Interaction of anthelmintic benzimidazoles with Ascaris suum embryonic tubulin. (1980). https://pubmed.ncbi.nlm.nih.gov/7388055/ DOI: 10.1016/0304-4165(80)90431-6
Complete structured claim and evidence
Where it participates (unsigned role)
In vitro incubation of Ascaris suum with 10 micromolar mebendazole resulted in a complete loss of colchicine binding ability of extracts obtained from the parasite intestine, the colchicine binding receptor in those extracts was identified biochemically as tubulin, and that protein comprised approximately 0.8% of the soluble intestinal protein.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/mebendazole-research/7335116.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "358adb37f881bf9fc64cf4cea24ce690792e958df702a705b2addda3295ad144", "start_char": 0, "end_char": 1621, "text_sha256": "358adb37f881bf9fc64cf4cea24ce690792e958df702a705b2addda3295ad144"}
- experimental_model
- Colchicine and tritiated mebendazole binding to partially purified tubulin from Ascaris suum intestine and porcine brain
- exposure
- In vitro incubation of Ascaris suum with 10 micromolar mebendazole, with tubulin partially purified from the intestine
- limitations
- Measures the tissue mebendazole actually damages rather than embryonic tissue, and reaches the opposite conclusion about selectivity. Solubility prevented a precise association constant for mebendazole itself.
- 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
- Nematode and pig
- plain_language
- In the gut of the worm, the drug wipes out the protein it is supposed to act on.
- primary_references
- [mbz-p7335116] Intestinal tubulin as possible target for the chemotherapeutic action of mebendazole in parasitic nematodes. (1981). https://pubmed.ncbi.nlm.nih.gov/7335116/ DOI: 10.1016/0166-6851(81)90064-5
- tissue_or_cell_type
- Nematode intestinal tubulin and porcine brain tubulin
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Colchicine and tritiated mebendazole binding to partially purified tubulin from Ascaris suum intestine and porcine brain · source_derived_draft · unverified_draft
### mbz-intestinal-tubulin-is-the-target In vitro incubation of Ascaris suum with 10 micromolar mebendazole resulted in a complete loss of colchicine binding ability of extracts obtained from the parasite intestine, the colchicine binding receptor in those extracts was identified biochemically as tubulin, and that protein comprised approximately 0.8% of the soluble intestinal protein. 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 the gut of the worm, the drug wipes out the protein it is supposed to act on. organism: Nematode and pig tissue_or_cell_type: Nematode intestinal tubulin and porcine brain tubulin experimental_model: Colchicine and tritiated mebendazole binding to partially purified tubulin from Ascaris suum intestine and porcine brain limitations: Measures the tissue mebendazole actually damages rather than embryonic tissue, and reaches the opposite conclusion about selectivity. Solubility prevented a precise association constant for mebendazole itself. exposure: In vitro incubation of Ascaris suum with 10 micromolar mebendazole, with tubulin partially purified from the intestine evidence_span: {"source_cache": "artifacts/mebendazole-research/7335116.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "358adb37f881bf9fc64cf4cea24ce690792e958df702a705b2addda3295ad144", "start_char": 0, "end_char": 1621, "text_sha256": "358adb37f881bf9fc64cf4cea24ce690792e958df702a705b2addda3295ad144"} [mbz-p7335116] Intestinal tubulin as possible target for the chemotherapeutic action of mebendazole in parasitic nematodes. (1981). https://pubmed.ncbi.nlm.nih.gov/7335116/ DOI: 10.1016/0166-6851(81)90064-5
Complete structured claim and evidenceThe inhibition constants of mebendazole and fenbendazole for Ascaris suum embryonic tubulin were 1.9 x 10-8 and 6.5 x 10-8 molar while those for bovine brain tubulin were 7.3 x 10-6 and 1.7 x 10-5 molar, values 250 to 400 times greater, so that differential binding affinities between nematode and mammalian tubulin may explain the selective toxicity.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/mebendazole-research/7388055.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5613d7fb281b4fd39b17bfdbafaf0ea823fb63b928048a9dd112fb71bf4cd2b7", "start_char": 0, "end_char": 1209, "text_sha256": "5613d7fb281b4fd39b17bfdbafaf0ea823fb63b928048a9dd112fb71bf4cd2b7"}
- experimental_model
- Inhibition of tritiated colchicine binding to cytosolic tubulin from 8-day Ascaris suum embryos and from bovine brain
- exposure
- Mebendazole and fenbendazole compared on the two tubulins in the same assay
- limitations
- The founding selectivity result. It measures embryonic tubulin; the study in this collection that measured intestinal tubulin found a far smaller difference.
- 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
- Nematode and cattle
- plain_language
- The drug grips worm tubulin hundreds of times more tightly than ours, which is the usual explanation for why it is safe.
- primary_references
- [mbz-p7388055] Interaction of anthelmintic benzimidazoles with Ascaris suum embryonic tubulin. (1980). https://pubmed.ncbi.nlm.nih.gov/7388055/ DOI: 10.1016/0304-4165(80)90431-6
- tissue_or_cell_type
- Embryonic nematode tubulin and bovine brain tubulin
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inhibition of tritiated colchicine binding to cytosolic tubulin from 8-day Ascaris suum embryos and from bovine brain · source_derived_draft · unverified_draft
### mbz-selectivity-250-fold The inhibition constants of mebendazole and fenbendazole for Ascaris suum embryonic tubulin were 1.9 x 10-8 and 6.5 x 10-8 molar while those for bovine brain tubulin were 7.3 x 10-6 and 1.7 x 10-5 molar, values 250 to 400 times greater, so that differential binding affinities between nematode and mammalian tubulin may explain the selective toxicity. 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 drug grips worm tubulin hundreds of times more tightly than ours, which is the usual explanation for why it is safe. organism: Nematode and cattle tissue_or_cell_type: Embryonic nematode tubulin and bovine brain tubulin experimental_model: Inhibition of tritiated colchicine binding to cytosolic tubulin from 8-day Ascaris suum embryos and from bovine brain limitations: The founding selectivity result. It measures embryonic tubulin; the study in this collection that measured intestinal tubulin found a far smaller difference. exposure: Mebendazole and fenbendazole compared on the two tubulins in the same assay evidence_span: {"source_cache": "artifacts/mebendazole-research/7388055.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5613d7fb281b4fd39b17bfdbafaf0ea823fb63b928048a9dd112fb71bf4cd2b7", "start_char": 0, "end_char": 1209, "text_sha256": "5613d7fb281b4fd39b17bfdbafaf0ea823fb63b928048a9dd112fb71bf4cd2b7"} [mbz-p7388055] Interaction of anthelmintic benzimidazoles with Ascaris suum embryonic tubulin. (1980). https://pubmed.ncbi.nlm.nih.gov/7388055/ DOI: 10.1016/0304-4165(80)90431-6
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.