Mammalian brain tubulin

evidence_span

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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

evidence_span

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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/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

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 602–613

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

evidence_span

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experimental_model

Correlation of Haemonchus contortus egg hatch inhibition with inhibition of mammalian tubulin polymerisation

exposure

Benzimidazole carbamates tested in both assays

limitations

A correlation rather than a demonstration of mechanism in the egg, and the hatch assay was sensitive to co-solvent concentration and incubation time.

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 compounds that block tubulin are the ones that stop eggs hatching, and the ones that do not, do not.

primary_references

[mbz-p3564338] Comparison of inhibition of polymerisation of mammalian tubulin and helminth ovicidal activity by benzimidazole carbamates. (1987). https://pubmed.ncbi.nlm.nih.gov/3564338/ DOI: 10.1016/0304-4017(87)90029-x

tissue_or_cell_type

Nematode eggs and mammalian 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 212–223

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Correlation of Haemonchus contortus egg hatch inhibition with inhibition of mammalian tubulin polymerisation · source_derived_draft · unverified_draft

### mbz-egg-hatch-tracks-tubulin Benzimidazole carbamates with strong inhibitory activity against mammalian tubulin were potent inhibitors of Haemonchus contortus egg hatch while non-inhibitors failed to prevent hatching, supporting the view that the primary mode of action of these drugs on nematode eggs is inhibition of microtubule-dependent processes within the developing egg. 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 compounds that block tubulin are the ones that stop eggs hatching, and the ones that do not, do not. organism: Nematode and mammal tissue_or_cell_type: Nematode eggs and mammalian tubulin experimental_model: Correlation of Haemonchus contortus egg hatch inhibition with inhibition of mammalian tubulin polymerisation limitations: A correlation rather than a demonstration of mechanism in the egg, and the hatch assay was sensitive to co-solvent concentration and incubation time. exposure: Benzimidazole carbamates tested in both assays evidence_span: {"source_cache": "artifacts/mebendazole-research/3564338.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "89495a42e9f41cac9010e20e925b802c27fde1dfac9a4a24dd2236335f4d61b1", "start_char": 0, "end_char": 818, "text_sha256": "89495a42e9f41cac9010e20e925b802c27fde1dfac9a4a24dd2236335f4d61b1"} [mbz-p3564338] Comparison of inhibition of polymerisation of mammalian tubulin and helminth ovicidal activity by benzimidazole carbamates. (1987). https://pubmed.ncbi.nlm.nih.gov/3564338/ DOI: 10.1016/0304-4017(87)90029-x

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

evidence_span

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experimental_model

Turbidimetric microtubule polymerisation assay and colchicine binding assay on purified bovine brain tubulin

exposure

Eleven benzimidazoles compared for inhibition of the initial rate of microtubule polymerisation

limitations

Purified mammalian tubulin, which is the off-target rather than the parasite target. It fixes where mebendazole sits in the class by potency.

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

Cattle

plain_language

Mebendazole sits in the potent group; thiabendazole is about a hundred times weaker.

primary_references

[mbz-p728472] Interaction of anthelmintic benzimidazoles and benzimidazole derivatives with bovine brain tubulin. (1978). https://pubmed.ncbi.nlm.nih.gov/728472/ DOI: 10.1016/0304-4165(78)90334-3

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 82–93

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Turbidimetric microtubule polymerisation assay and colchicine binding assay on purified bovine brain tubulin · source_derived_draft · unverified_draft

### mbz-inhibits-polymerisation Median inhibitory concentrations for nocodazole, oxibendazole, parbendazole, mebendazole and fenbendazole against bovine brain tubulin polymerisation ranged from 1.97 x 10-6 to 6.32 x 10-6 molar, while benomyl, cambendazole and carbendazim had values from 5.83 x 10-5 to 9.01 x 10-5 molar and thiabendazole had a value of 5.49 x 10-4 molar. 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: Mebendazole sits in the potent group; thiabendazole is about a hundred times weaker. organism: Cattle tissue_or_cell_type: Brain tubulin experimental_model: Turbidimetric microtubule polymerisation assay and colchicine binding assay on purified bovine brain tubulin limitations: Purified mammalian tubulin, which is the off-target rather than the parasite target. It fixes where mebendazole sits in the class by potency. exposure: Eleven benzimidazoles compared for inhibition of the initial rate of microtubule polymerisation evidence_span: {"source_cache": "artifacts/mebendazole-research/728472.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "544c36409218c93ebff76d932a2bc6e14ccf7fd6e217d4614c4b561281c2555a", "start_char": 0, "end_char": 1025, "text_sha256": "544c36409218c93ebff76d932a2bc6e14ccf7fd6e217d4614c4b561281c2555a"} [mbz-p728472] Interaction of anthelmintic benzimidazoles and benzimidazole derivatives with bovine brain tubulin. (1978). https://pubmed.ncbi.nlm.nih.gov/728472/ DOI: 10.1016/0304-4165(78)90334-3

evidence_span

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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

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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

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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

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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

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experimental_model

Concentration-matched comparison of viability, microtubule polymerisation and metaphase arrest, with NCI COMPARE analysis and a head-to-head animal comparison against vincristine

exposure

Mebendazole against vincristine close to its maximum tolerated dose in orthotopic GL261 tumours

limitations

Tests whether the anticancer effect is the microtubule effect by matching concentrations across three assays, which most repurposing studies do not do.

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

Mouse

plain_language

The concentration that kills the cell is the concentration that blocks its microtubules, so it is the same mechanism.

primary_references

[mbz-p28386621] Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors. (2017). https://pubmed.ncbi.nlm.nih.gov/28386621/ DOI: 10.2119/molmed.2017.00011

tissue_or_cell_type

Glioblastoma

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 498–509

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Concentration-matched comparison of viability, microtubule polymerisation and metaphase arrest, with NCI COMPARE analysis and a head-to-head animal comparison against vincristine · source_derived_draft · unverified_draft

### mbz-the-anticancer-effect-is-tubulin The effective concentrations of mebendazole to inhibit GL261 glioblastoma cell viability, microtubule polymerization and metaphase arrest were very similar, and using mebendazole as a seed for the NCI COMPARE program revealed that the top-scoring drugs were highly enriched in microtubule-targeting drugs, indicating that the cell toxicity of mebendazole is indeed caused by inhibiting microtubule formation. 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 concentration that kills the cell is the concentration that blocks its microtubules, so it is the same mechanism. organism: Mouse tissue_or_cell_type: Glioblastoma experimental_model: Concentration-matched comparison of viability, microtubule polymerisation and metaphase arrest, with NCI COMPARE analysis and a head-to-head animal comparison against vincristine limitations: Tests whether the anticancer effect is the microtubule effect by matching concentrations across three assays, which most repurposing studies do not do. exposure: Mebendazole against vincristine close to its maximum tolerated dose in orthotopic GL261 tumours evidence_span: {"source_cache": "artifacts/mebendazole-research/28386621.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "20ef610d6b4a341f8a0a3f731bbea5477badbee517062c303bbf1075f3a29865", "start_char": 0, "end_char": 1788, "text_sha256": "20ef610d6b4a341f8a0a3f731bbea5477badbee517062c303bbf1075f3a29865"} [mbz-p28386621] Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors. (2017). https://pubmed.ncbi.nlm.nih.gov/28386621/ DOI: 10.2119/molmed.2017.00011