Benomyl

Where it participates (unsigned role)

1. 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.

   Beta-tubulin carrying tyrosine at position 200 → Resistance to benzimidazole anthelmintics source_derived_draftungraded
   Experimental context and source evidence

   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

   Complete structured claim and evidence

2. Changing Saccharomyces cerevisiae beta-tubulin residue phenylalanine 167 to tyrosine produced at least 3 to 4 fold decreased sensitivity to carbendazim and nocodazole and the mutant was cold sensitive, implying a direct effect on benzimidazole binding rather than a nonspecific increase in microtubule stability, but surprisingly the mutant had 8 fold increased sensitivity to benomyl, which is structurally identical to carbendazim except at position 1, suggesting that residue 167 interacts with benzimidazoles in the vicinity of the 1 position.

   Beta-tubulin carrying tyrosine at position 167 → Resistance to benzimidazole anthelmintics source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/mebendazole-research/8641470.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "35145959fc480be6039e088de374d7549dddc6f298511a41d2a760e7fdb8f455", "start_char": 0, "end_char": 917, "text_sha256": "35145959fc480be6039e088de374d7549dddc6f298511a41d2a760e7fdb8f455"}

   experimental_model

   Site-directed mutagenesis and gene replacement of Saccharomyces cerevisiae beta-tubulin residue 167

   exposure

   Phenylalanine 167 changed to tyrosine, then tested against carbendazim, nocodazole and benomyl

   limitations

   A clean genetic test in a tractable organism, and the cold sensitivity argues the effect is on binding rather than on general microtubule stability. Yeast beta-tubulin is not nematode beta-tubulin.

   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

   Yeast

   plain_language

   The same mutation that resists one compound makes the organism more vulnerable to its near twin.

   primary_references

   [mbz-p8641470] Site-directed mutagenesis of Saccharomyces cerevisiae beta-tubulin: interaction between residue 167 and benzimidazole compounds. (1996). https://pubmed.ncbi.nlm.nih.gov/8641470/ DOI: 10.1016/0014-5793(96)00334-1

   tissue_or_cell_type

   Beta-tubulin

   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 303–314

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutagenesis and gene replacement of Saccharomyces cerevisiae beta-tubulin residue 167 · source_derived_draft · unverified_draft

   ### mbz-tyr167-and-negative-effect Changing Saccharomyces cerevisiae beta-tubulin residue phenylalanine 167 to tyrosine produced at least 3 to 4 fold decreased sensitivity to carbendazim and nocodazole and the mutant was cold sensitive, implying a direct effect on benzimidazole binding rather than a nonspecific increase in microtubule stability, but surprisingly the mutant had 8 fold increased sensitivity to benomyl, which is structurally identical to carbendazim except at position 1, suggesting that residue 167 interacts with benzimidazoles in the vicinity of the 1 position. 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: The same mutation that resists one compound makes the organism more vulnerable to its near twin. organism: Yeast tissue_or_cell_type: Beta-tubulin experimental_model: Site-directed mutagenesis and gene replacement of Saccharomyces cerevisiae beta-tubulin residue 167 limitations: A clean genetic test in a tractable organism, and the cold sensitivity argues the effect is on binding rather than on general microtubule stability. Yeast beta-tubulin is not nematode beta-tubulin. exposure: Phenylalanine 167 changed to tyrosine, then tested against carbendazim, nocodazole and benomyl evidence_span: {"source_cache": "artifacts/mebendazole-research/8641470.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "35145959fc480be6039e088de374d7549dddc6f298511a41d2a760e7fdb8f455", "start_char": 0, "end_char": 917, "text_sha256": "35145959fc480be6039e088de374d7549dddc6f298511a41d2a760e7fdb8f455"} [mbz-p8641470] Site-directed mutagenesis of Saccharomyces cerevisiae beta-tubulin: interaction between residue 167 and benzimidazole compounds. (1996). https://pubmed.ncbi.nlm.nih.gov/8641470/ DOI: 10.1016/0014-5793(96)00334-1

   Complete structured claim and evidence