The benzimidazole-tubulin complex

Where it participates (unsigned role)

1. 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.

   Mebendazole → Nematode beta-tubulin source_derived_draftungraded
   Experimental context and source evidence

   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

   Complete structured claim and evidence

2. 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.

   Mebendazole → Mammalian brain tubulin source_derived_draftungraded
   Experimental context and source evidence

   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

   Complete structured claim and evidence