Nematode beta-tubulin

evidence_span

{"source_cache": "artifacts/mebendazole-research/1741017.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dfdd18b65ab4df953ac012978b5c922824de051db3b5fab15bac4b97abbfb5c", "start_char": 0, "end_char": 1425, "text_sha256": "5dfdd18b65ab4df953ac012978b5c922824de051db3b5fab15bac4b97abbfb5c"}

experimental_model

Cloning and sequencing of three beta-tubulin cDNAs from Haemonchus contortus

exposure

Sequence comparison across nematode and mammalian beta-tubulins and across sensitive and resistant populations

limitations

Sequence work only. It states plainly that the molecular basis of the nematode versus mammalian difference is not known, which is still the open question in this chapter.

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

plain_language

The worm has several versions of this protein, and the differences from ours are known but not explained.

primary_references

[mbz-p1741017] Three beta-tubulin cDNAs from the parasitic nematode Haemonchus contortus. (1992). https://pubmed.ncbi.nlm.nih.gov/1741017/ DOI: 10.1016/0166-6851(92)90227-b

tissue_or_cell_type

Beta-tubulin genes

Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 290–301

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning and sequencing of three beta-tubulin cDNAs from Haemonchus contortus · source_derived_draft · unverified_draft

### mbz-more-than-one-isotype Three beta-tubulin cDNAs were cloned from Haemonchus contortus, two differing at only 23 nucleotides giving 4 amino acid changes and a third representing a different isotype class differing extensively in the carboxy terminus; comparison with mammalian beta-tubulins identified several regions of consistent difference whose functional significance has not been defined, and sequences very similar or identical to two of the clones were present in both benzimidazole-sensitive and benzimidazole-resistant populations although resistant organisms may differ in the presence of a gene product related to the third. 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 worm has several versions of this protein, and the differences from ours are known but not explained. organism: Nematode tissue_or_cell_type: Beta-tubulin genes experimental_model: Cloning and sequencing of three beta-tubulin cDNAs from Haemonchus contortus limitations: Sequence work only. It states plainly that the molecular basis of the nematode versus mammalian difference is not known, which is still the open question in this chapter. exposure: Sequence comparison across nematode and mammalian beta-tubulins and across sensitive and resistant populations evidence_span: {"source_cache": "artifacts/mebendazole-research/1741017.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dfdd18b65ab4df953ac012978b5c922824de051db3b5fab15bac4b97abbfb5c", "start_char": 0, "end_char": 1425, "text_sha256": "5dfdd18b65ab4df953ac012978b5c922824de051db3b5fab15bac4b97abbfb5c"} [mbz-p1741017] Three beta-tubulin cDNAs from the parasitic nematode Haemonchus contortus. (1992). https://pubmed.ncbi.nlm.nih.gov/1741017/ DOI: 10.1016/0166-6851(92)90227-b

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

Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 121–132

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

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

Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 95–106

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

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

Measured in the worm’s gut rather than its embryos, the drug is only about twice as selective, which is not enough to explain its safety.

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

Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 134–145

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-selectivity-only-twofold Mebendazole inhibited colchicine binding to partially purified Ascaris suum intestinal tubulin competitively with an inhibition constant of 4.22 x 10-6 molar and inhibited colchicine binding to porcine brain tubulin competitively with an inhibition constant of 8.0 x 10-6 molar, so that in view of the small difference in drug binding abilities it remains unclear whether the selective toxicity can be solely explained by interference with the parasite microtubular system, and the authors suggest that differential pharmacokinetic behaviour between parasite and host may be the essential basis for the difference in susceptibility. 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: Measured in the worm’s gut rather than its embryos, the drug is only about twice as selective, which is not enough to explain its safety. 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

evidence_span

{"source_cache": "artifacts/mebendazole-research/1459788.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b34533a3360a1b113dca959ed53c0c5cf9f7efe61403c2b498146c90e7085bb1", "start_char": 0, "end_char": 1160, "text_sha256": "b34533a3360a1b113dca959ed53c0c5cf9f7efe61403c2b498146c90e7085bb1"}

experimental_model

Kinetic and equilibrium binding of tritiated mebendazole to tubulin from third-stage Haemonchus contortus larvae

exposure

Association and dissociation rate constants measured in partially purified preparations and crude cytosol

limitations

Separates the rate of binding from the rate of release, which an equilibrium measurement cannot. The kinetic and equilibrium constants differ about thirtyfold and the authors argue for the kinetic value.

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

plain_language

It binds worm tubulin quickly and then stays there; on ours it falls straight off again.

primary_references

[mbz-p1459788] The kinetics of mebendazole binding to Haemonchus contortus tubulin. (1992). https://pubmed.ncbi.nlm.nih.gov/1459788/ DOI: 10.1016/0020-7519(92)90051-l

tissue_or_cell_type

Larval nematode tubulin

Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 147–158

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetic and equilibrium binding of tritiated mebendazole to tubulin from third-stage Haemonchus contortus larvae · source_derived_draft · unverified_draft

### mbz-slow-release-is-the-point Association of tritiated mebendazole to Haemonchus contortus tubulin was rapid at 2.6 x 10(5) per molar per minute but dissociation was slow at 1.58 x 10(-3) per minute, giving a kinetic affinity constant of 1.6 x 10(8) per molar against an equilibrium estimate of 5.3 x 10(6) per molar, and the slow dissociation from nematode tubulin, which contrasts with rapid dissociation from mammalian tubulin, supports the view that selective toxicity results from a difference between the affinities of mammalian and nematode tubulins. 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 binds worm tubulin quickly and then stays there; on ours it falls straight off again. organism: Nematode tissue_or_cell_type: Larval nematode tubulin experimental_model: Kinetic and equilibrium binding of tritiated mebendazole to tubulin from third-stage Haemonchus contortus larvae limitations: Separates the rate of binding from the rate of release, which an equilibrium measurement cannot. The kinetic and equilibrium constants differ about thirtyfold and the authors argue for the kinetic value. exposure: Association and dissociation rate constants measured in partially purified preparations and crude cytosol evidence_span: {"source_cache": "artifacts/mebendazole-research/1459788.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b34533a3360a1b113dca959ed53c0c5cf9f7efe61403c2b498146c90e7085bb1", "start_char": 0, "end_char": 1160, "text_sha256": "b34533a3360a1b113dca959ed53c0c5cf9f7efe61403c2b498146c90e7085bb1"} [mbz-p1459788] The kinetics of mebendazole binding to Haemonchus contortus tubulin. (1992). https://pubmed.ncbi.nlm.nih.gov/1459788/ DOI: 10.1016/0020-7519(92)90051-l

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

Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 108–119

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

evidence_span

{"source_cache": "artifacts/mebendazole-research/6712717.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dc6664076b62c0da221cce8e34690f297828b832da76857a2cc12cf9769fb282", "start_char": 0, "end_char": 949, "text_sha256": "dc6664076b62c0da221cce8e34690f297828b832da76857a2cc12cf9769fb282"}

experimental_model

In vitro polymerisation of tubulin purified from Ascaridia galli and from mammalian tissue, with electron microscopy

exposure

Colchicine and a range of anthelmintic benzimidazoles on both tubulins

limitations

Adds electron microscopy, which shows the drug reduces the number and length of microtubules without making abnormal ones. Purified protein rather than intact 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

Nematode and mammal

plain_language

The microtubules that do form look normal; there are simply fewer and shorter ones.

primary_references

[mbz-p6712717] A comparison of the interaction of anthelmintic benzimidazoles with tubulin isolated from mammalian tissue and the parasitic nematode Ascaridia galli. (1984). https://pubmed.ncbi.nlm.nih.gov/6712717/ DOI: 10.1016/0006-2952(84)90515-x

tissue_or_cell_type

Purified tubulin

Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 173–184

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vitro polymerisation of tubulin purified from Ascaridia galli and from mammalian tissue, with electron microscopy · source_derived_draft · unverified_draft

### mbz-fewer-not-abnormal Colchicine and a range of anthelmintic benzimidazoles inhibited in vitro polymerisation of tubulin purified from Ascaridia galli more than that purified from mammalian tissue, with oxfendazole and thiabendazole having virtually no effect on mammalian tubulin assembly while both inhibited nematode tubulin, and electron microscopy revealed no morphological differences between microtubules polymerised with or without drug although their length and number were reduced. 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 microtubules that do form look normal; there are simply fewer and shorter ones. organism: Nematode and mammal tissue_or_cell_type: Purified tubulin experimental_model: In vitro polymerisation of tubulin purified from Ascaridia galli and from mammalian tissue, with electron microscopy limitations: Adds electron microscopy, which shows the drug reduces the number and length of microtubules without making abnormal ones. Purified protein rather than intact parasite. exposure: Colchicine and a range of anthelmintic benzimidazoles on both tubulins evidence_span: {"source_cache": "artifacts/mebendazole-research/6712717.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dc6664076b62c0da221cce8e34690f297828b832da76857a2cc12cf9769fb282", "start_char": 0, "end_char": 949, "text_sha256": "dc6664076b62c0da221cce8e34690f297828b832da76857a2cc12cf9769fb282"} [mbz-p6712717] A comparison of the interaction of anthelmintic benzimidazoles with tubulin isolated from mammalian tissue and the parasitic nematode Ascaridia galli. (1984). https://pubmed.ncbi.nlm.nih.gov/6712717/ DOI: 10.1016/0006-2952(84)90515-x

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/mebendazole-research/7877171.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "091ba3ac445b68112bac29dec56d0d1a48e0d258714ebdbe090b5e7728e6ceaa", "start_char": 0, "end_char": 1532, "text_sha256": "091ba3ac445b68112bac29dec56d0d1a48e0d258714ebdbe090b5e7728e6ceaa"}

experimental_model

Heterologous expression of Haemonchus contortus beta-tubulin alleles in Caenorhabditis elegans ben-1 mutants

exposure

Parasite benzimidazole-sensitive and resistant alleles and in vitro mutagenised constructs, assayed with benomyl and thiabendazole

limitations

A functional test rather than an association: the alleles were put into a resistant host and the phenotype followed the codon. The assay drugs were benomyl and thiabendazole rather than mebendazole.

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

plain_language

Swapping one amino acid back made resistant worms susceptible again, which makes it the cause and not a coincidence.

primary_references

[mbz-p7877171] Beta-tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. (1995). https://pubmed.ncbi.nlm.nih.gov/7877171/ DOI: 10.1006/jmbi.1994.0102

tissue_or_cell_type

Beta-tubulin isotype 1

trigger_kind

machinery_impairment Imported condition classification; unverified.

Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 264–275

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous expression of Haemonchus contortus beta-tubulin alleles in Caenorhabditis elegans ben-1 mutants · source_derived_draft · unverified_draft

### mbz-phe200-causes-resistance All Haemonchus contortus tub-1 constructs encoding phenylalanine at position 200 conferred susceptibility to thiabendazole in benzimidazole-resistant Caenorhabditis elegans ben-1 mutants, whereas constructs carrying tyrosine at position 200 did not alter the resistant phenotype, leading to the conclusion that the single phenylalanine to tyrosine mutation at position 200 in beta-tubulin isotype 1 is the cause of benzimidazole resistance in Haemonchus contortus. Condition category: machinery_impairment 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: Swapping one amino acid back made resistant worms susceptible again, which makes it the cause and not a coincidence. organism: Nematode tissue_or_cell_type: Beta-tubulin isotype 1 experimental_model: Heterologous expression of Haemonchus contortus beta-tubulin alleles in Caenorhabditis elegans ben-1 mutants limitations: A functional test rather than an association: the alleles were put into a resistant host and the phenotype followed the codon. The assay drugs were benomyl and thiabendazole rather than mebendazole. exposure: Parasite benzimidazole-sensitive and resistant alleles and in vitro mutagenised constructs, assayed with benomyl and thiabendazole evidence_span: {"source_cache": "artifacts/mebendazole-research/7877171.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "091ba3ac445b68112bac29dec56d0d1a48e0d258714ebdbe090b5e7728e6ceaa", "start_char": 0, "end_char": 1532, "text_sha256": "091ba3ac445b68112bac29dec56d0d1a48e0d258714ebdbe090b5e7728e6ceaa"} [mbz-p7877171] Beta-tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. (1995). https://pubmed.ncbi.nlm.nih.gov/7877171/ DOI: 10.1006/jmbi.1994.0102

evidence_span

{"source_cache": "artifacts/mebendazole-research/1554382.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "70fec1c41b747eaae6d4a47ad1075a49828ee942f7935b85eb0f51416cd57c37", "start_char": 0, "end_char": 1495, "text_sha256": "70fec1c41b747eaae6d4a47ad1075a49828ee942f7935b85eb0f51416cd57c37"}

experimental_model

Tritiated benzimidazole carbamate binding to mammalian brain tubulin measured at 4 and 37 degrees

exposure

Mebendazole, oxibendazole, oxfendazole and carbendazim binding measured across temperature

limitations

The temperature arm is what makes this decisive: it explains why the same drug behaves differently on host and parasite tubulin at body temperature. Binding was measured on brain tubulin, not on tubulin from a target 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

Mammal

plain_language

At body temperature the drug slides off our tubulin and locks onto the worm’s; cool ours down and it sticks to that too.

primary_references

[mbz-p1554382] Binding of [3H]benzimidazole carbamates to mammalian brain tubulin and the mechanism of selective toxicity of the benzimidazole anthelmintics. (1992). https://pubmed.ncbi.nlm.nih.gov/1554382/ DOI: 10.1016/0006-2952(92)90617-r

tissue_or_cell_type

Brain tubulin

Mebendazole: the tubulin it binds, why that is selective, the crystal form that decides whether any of it works, and the off-target that became an oncology programme (2026-09-22) · lines 160–171

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tritiated benzimidazole carbamate binding to mammalian brain tubulin measured at 4 and 37 degrees · source_derived_draft · unverified_draft

### mbz-temperature-decides Tritiated benzimidazole carbamate binding to mammalian brain tubulin was markedly greater at 4 degrees than at 37 degrees for all ligands, association constants and maximum binding were temperature dependent, and the first order dissociation rate constant of the mebendazole-tubulin complex was reduced by two orders of magnitude at 4 degrees compared with 37 degrees, suggesting that temperature-induced conformational changes in the tubulin dimer influence the ability to form a stable complex; this is unlike the interaction observed for parasitic nematodes where optimum binding occurs at 37 degrees and results in a pseudo-irreversible complex. 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: At body temperature the drug slides off our tubulin and locks onto the worm’s; cool ours down and it sticks to that too. organism: Mammal tissue_or_cell_type: Brain tubulin experimental_model: Tritiated benzimidazole carbamate binding to mammalian brain tubulin measured at 4 and 37 degrees limitations: The temperature arm is what makes this decisive: it explains why the same drug behaves differently on host and parasite tubulin at body temperature. Binding was measured on brain tubulin, not on tubulin from a target tissue. exposure: Mebendazole, oxibendazole, oxfendazole and carbendazim binding measured across temperature evidence_span: {"source_cache": "artifacts/mebendazole-research/1554382.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "70fec1c41b747eaae6d4a47ad1075a49828ee942f7935b85eb0f51416cd57c37", "start_char": 0, "end_char": 1495, "text_sha256": "70fec1c41b747eaae6d4a47ad1075a49828ee942f7935b85eb0f51416cd57c37"} [mbz-p1554382] Binding of [3H]benzimidazole carbamates to mammalian brain tubulin and the mechanism of selective toxicity of the benzimidazole anthelmintics. (1992). https://pubmed.ncbi.nlm.nih.gov/1554382/ DOI: 10.1016/0006-2952(92)90617-r