AntibioticMech

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cycloheximide

CHEBI:27641 ·resolve ·ANTIFUNGAL ·EXACT REVIEWED

A dicarboximide that is 4-(2-hydroxyethyl)piperidine-2,6-dione in which one of the hydrogens attached to the carbon bearing the hydroxy group is replaced by a 3,5-dimethyl-2-oxocyclohexyl group. It is an antibiotic produced by the bacterium Streptomyces griseus. — ChEBI

Classification

antibiotic without defined classificationARO:3000003

Strictly broader compounds or drug classes this molecule belongs to.

Chemical structure

Computed structure properties
Molecular formulaC15H23NO4
Charge0
Average mass281.352 Da
Monoisotopic mass281.16271 Da
SourceChEBI
InChIKeyYPHMISFOHDHNIV-FSZOTQKASA-N

SMILES

[H][C@@]1([C@H](O)CC2CC(=O)NC(=O)C2)C[C@@H](C)C[C@H](C)C1=O

InChI

InChI=1S/C15H23NO4/c1-8-3-9(2)15(20)11(4-8)12(17)5-10-6-13(18)16-14(19)7-10/h8-12,17H,3-7H2,1-2H3,(H,16,18,19)/t8-,9-,11-,12+/m0/s1

Also called

Cross-references

Identifiers for this same structure in other resources. An accession that lands on two different structures in this corpus is withheld from both rather than shown here, since it names at most one of them.

Drug registries

Identifiers that name a drug rather than a structure. One of these can cover a parent compound, its salts and its stereoisomers, which this corpus keeps as separate records, so it is not an equivalence of structure.

Patents and articles

Documents about this compound. A patent covers a class and an article covers a topic; neither identifies a structure.

Activity roles

Every antimicrobial role a source asserts for this compound — the unreduced evidence behind its antimicrobial_class.

Source concepts

Every upstream concept that resolved to this record. The merge is the product: this is what shows ChEBI and CARD are describing the same structure.

Upstream concepts merged into this record
SourceNative IDLabelMinted CURIEVersion
ARO ARO:3009188 cycloheximide antibioticmech:aro-eb6ceb3794 2026-08-30
CHEBI CHEBI:27641 cycloheximide antibioticmech:chebi-122ccc7d98 2026-08-30

Molecular targets

The molecular entity or process this compound acts on. Each target carries evidence — this is a mechanistic claim, not a classification.

ribosomal complex PROTEIN_COMPLEX DIRECT_BINDING_TARGET

ARO:3000729

CARD/ARO database assertion; target organism, strain, and assay are not specified. ARO asserts stabilization of the ribosomal complex by antibiotics. Evidence status: PRIMARY_EVIDENCE_NEEDED. Source: CARD_ARO 2026-08-30 (retrieved 2026-08-30).

eukaryotic 80S ribosome PROTEIN_COMPLEX DIRECT_BINDING_TARGET

High-resolution inhibitor-ribosome X-ray structures directly located cycloheximide at an mRNA/tRNA-associated site; kinetic experiments supported its translation-elongation model. Evidence status: PRIMARY_EVIDENCE. Source: PRIMARY_LITERATURE 2014-09 (retrieved 2026-09-02).

Saccharomyces cerevisiae NCBITaxon:4932

Organism-specific examples
ProteinGeneOrganismEntry
Large ribosomal subunit protein uL15 UniProtKB:P02406
60S ribosomal E-site protein uL15 (RPL28; historical CYH2/L29) that lines the cycloheximide binding pocket with 25S rRNA in the S. cerevisiae 80S ribosome-inhibitor crystal structure (PMID:25209664, PDB 4U3U; S288c reference strain context).		 RPL28 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) NCBITaxon:559292 REVIEWED

Mechanism summary

Mode of action
PROTEIN_SYNTHESIS_INHIBITION host shared target — CURATOR: PMID:25209664 reports high-resolution structures of Saccharomyces cerevisiae 80S ribosomes with cycloheximide and kinetic experiments supporting inhibition of eukaryotic translation elongation.

Resistance mechanisms

5 source-backed resistance determinants or associations, with ARO grounding where reported. Grouped by reported mechanism type.

ANTIBIOTIC_TARGET_ALTERATION 2
ANTIBIOTIC_TARGET_ALTERATION
DeterminantARO IDOrganismGene familiesEvidence
CYH2/RPL28-associated laboratory cycloheximide resistance
Historical CYH2/L29 maps to current RPL28/uL15, not modern RPL29/eL29. Gene-level laboratory evidence does not establish direct drug binding to this protein. Historical variant coordinates remain unresolved; reference identity is not an experimental allele assignment.		 — Saccharomyces cerevisiae NCBITaxon:4932 RPL28
  • PMID:6304624 (Selected Results and Discussion, pp. 3125 and 3132; DOI:10.1093/nar/11.10.3123. Author-uploaded primary text inspected; native figures not inspected.)
  • UniProtKB:P02406 (Reference identity only: RPL28, YGL103W; UniProtKB 2026_03, entry 210, sequence 3. S288c NCBITaxon:559292 is reference context, not an experimental strain assignment.)
Laboratory genetic and protein comparisons
Saccharomyces cerevisiae ACT1 with mutations conferring resistance to cycloheximide ARO:3009326 not organism-specific —
  • ARO:3009326 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3009188 (cycloheximide); database assertion, not a primary citation.)
UNKNOWN 2
UNKNOWN
DeterminantARO IDOrganismGene familiesEvidence
AGP2-associated laboratory cycloheximide resistance
Laboratory phenotype association. PDR5-mediated causality and direct cycloheximide transport by Agp2 were not established. Figure 1B units conflict with Results; no numerical AST imported. Reference identity is not an experimental allele assignment.		 — Saccharomyces cerevisiae NCBITaxon:4932 AGP2
  • DOI:10.1371/journal.pone.0303747 (Results and Discussion; native Figures 1, 8 and 10 inspected, pp. 7, 15 and 19.)
  • UniProtKB:P38090 (Reference identity only: AGP2, YBR132C; UniProtKB 2026_03, entry 177, sequence 1. S288c NCBITaxon:559292 is reference context, not an experimental strain assignment.)
Comparative plate and liquid growth
STS1+ (wild type) [Overexpression] associated with resistance to cycloheximide
This is a curated gene-alteration/chemical resistance association, not evidence for a specific biochemical resistance mechanism. Grounding review bissinger-kuchler-1994-sts1-name-collision: Historical STS1 denotes PDR5, not the modern STS1 proteasome-tether gene. UniProtKB:P33302 / YOR153W supports the PDR5 reference crosswalk, not an exact experimental allele. The strain label is parent-background context; S288c is a reference, not a resolved experimental subject. Reference-only source identifiers: strain_taxon_id=NCBITaxon:559292. Rejected misassigned source identifiers: protein_accession=UniProtKB:P38637; gene_id=YIR011C_mRNA.		 — Saccharomyces cerevisiae NCBITaxon:4932
strain YPH501
PHIPO:0000544		 —
  • PMID:8307980 (PHI-base primary-literature antimicrobial interaction PHIG:1805; joined to this record by exact ChEBI identifier.)
  • DOI:10.1016/S0021-9258(17)41760-1 (Identifier-scope review: pp. 4180-4181: gene identity and strain context, Results and Table I, p. 4185: STS1/PDR5 allelism, UniProtKB release 2026_03: P33302 entry 235, P38637 entry 160, sequence versions 1. Reviewed 2026-10-08 by codex; curation/phibase_grounding_reviews.json SHA-256 1f5d50346b2916fce10969afa8d6409ea836dd15e8cf7fe3cfa3a78d6289b4ed.)
Cell growth assay
ANTIBIOTIC_EFFLUX 1
ANTIBIOTIC_EFFLUX
DeterminantARO IDOrganismGene familiesEvidence
Trychophyton rubrum MFS1 with mutations conferring resistance against cyclohexamide ARO:3009291 not organism-specific —
  • ARO:3009291 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3009188 (cycloheximide); database assertion, not a primary citation.)

Record-level evidence

Curation history

  1. SEEDED_FROM_SOURCES 2026-08-30 · seed_from_sources

    Seeded from data/raw/ inventories (ARO, CHEBI)

  2. RESEEDED_FROM_SOURCES 2026-08-30 · seed_from_sources

    Re-seeded from updated data/raw/ inventories

  3. RESEEDED_FROM_SOURCES 2026-08-30 · seed_from_sources

    Re-seeded from updated data/raw/ inventories

  4. RESEEDED_FROM_SOURCES 2026-08-31 · seed_from_sources

    Re-seeded from updated data/raw/ inventories

  5. RESEEDED_FROM_SOURCES 2026-09-02 · seed_from_sources

    Re-seeded from updated data/raw/ inventories

  6. RESEEDED_FROM_SOURCES 2026-09-02 · seed_from_sources

    Re-seeded from updated data/raw/ inventories

  7. REVIEWED 2026-09-02 · codex · LLM-assisted

    Verified exact ChEBI identity, structure, roles, and filing class; curator-confirmed eukaryotic protein-synthesis inhibition and added a primary-evidence 80S target while preserving the imported CARD target.

  8. RESEEDED_FROM_SOURCES 2026-09-03 · seed_from_sources

    Re-seeded from updated data/raw/ inventories

  9. RESEEDED_FROM_SOURCES 2026-09-03 · seed_from_sources

    Re-seeded from updated data/raw/ inventories

  10. RESEEDED_FROM_SOURCES 2026-09-10 · seed_from_sources

    Re-seeded from updated data/raw/ inventories

  11. REVIEWED_RESISTANCE_IDENTIFIER_SCOPE 2026-10-08 · codex · LLM-assisted

    Rejected the misassigned modern STS1 protein/locus for the historical PDR5 association; retained the supported reference crosswalk and withheld the unresolved experimental strain identifier without changing the source phenotype.

  12. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the whole-file PHI-base review checksum after additional reviews; all biological fields and previous identifier-scope decisions unchanged.

  13. REVIEWED_RESISTANCE_IDENTIFIER_SCOPE 2026-10-08 · codex · LLM-assisted

    Refreshed the whole-file PHI-base review checksum after the FKS1 review; all biological fields and previous identifier-scope decisions unchanged.

  14. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the whole-file PHI-base review checksum after two further reviews; all biological fields and previous identifier-scope decisions unchanged.

  15. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the whole-file PHI-base review checksum after Eddouzi subject reviews; all biological fields and prior decisions unchanged.

  16. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the whole-file PHI-base review checksum after Rybak reference-context reviews; all biological fields and previous decisions unchanged.

  17. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the whole-file PHI-base review checksum after carboxin reference-context reviews; all biological fields, activities and previous decisions unchanged.

  18. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the whole-file PHI-base review checksum after two additional carboxin identifier-scope corrections; all biological fields, activities and previous decisions unchanged.

  19. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the whole-file PHI-base review checksum after eleven additional identifier-scope corrections; biological fields, activities and decisions unchanged.

  20. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the whole-file PHI-base review checksum after seventeen additional identifier-scope corrections; biological fields, activities and decisions unchanged.

  21. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the whole-file PHI-base review checksum after one yeast identity-scope correction; biological fields, activities and prior decisions unchanged.

  22. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the whole-file PHI-base review checksum after twelve reference-scope corrections; biological fields, activities and prior decisions unchanged.

  23. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the shared PHI-base review checksum after nine identifier-scope corrections; previous decisions, biological fields and activities unchanged.

  24. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the shared PHI-base review checksum after six identifier-scope corrections; previous decisions, biological fields and activities unchanged.

  25. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed the shared PHI-base review checksum after eight subject-identity corrections; previous decisions, biological fields and activities unchanged.

  26. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed shared PHI-base review checksum after the Darlington subject correction; prior review decisions, biological fields and activities unchanged.

  27. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed shared PHI-base review checksum after the Nakayama reference-scope review; prior decisions, biological fields and activities unchanged.

  28. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed shared PHI-base review checksum after the Duan reference-scope review; prior decisions, biological fields and activities unchanged.

  29. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed shared PHI-base review checksum after the Piotrowska parent-reference review; prior decisions, biological fields and activities unchanged.

  30. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed shared PHI-base review checksum after the Xu subject and species corrections; prior decisions, biological fields and activities unchanged.

  31. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed shared PHI-base review checksum after the Shima parent-reference review; prior decisions, biological fields and activities unchanged.

  32. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed shared PHI-base review checksum after the Mehrabi parent-reference review; prior decisions, biological fields and activities unchanged.

  33. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-08 · codex · LLM-assisted

    Refreshed shared PHI-base review checksum after the Huang parent-reference review; prior decisions, biological fields and activities unchanged.

  34. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-09 · codex · LLM-assisted

    Refreshed shared PHI-base review checksum after the HDF1 subject-reference review; prior decisions, biological fields and activities unchanged.

  35. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-09 · codex · LLM-assisted

    Refreshed shared PHI-base review checksum after the Fouche parent-cohort review; prior decisions, biological fields and activities unchanged.

  36. REVIEWED_RESISTANCE_REFERENCE_CONTEXT 2026-10-09 · codex · LLM-assisted

    Refreshed shared PHI-base review checksum after the SDH8 reference-alias correction; prior decisions, biological fields and activities unchanged.

  37. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-09 · codex · LLM-assisted

    Refreshed the shared PHI-base review checksum after the Posteraro subject-context review; previous decisions, biological fields and activities unchanged.

  38. REVIEWED_RESISTANCE_REFERENCE_CONTEXT 2026-10-12 · codex · LLM-assisted

    Refreshed the shared PHI-base review checksum after four reference-identifier scope corrections; previous decisions, biological fields and activities unchanged.

  39. CURATED_RESISTANCE_EVIDENCE 2026-10-13 · codex · LLM-assisted

    Added qualified CYH2/RPL28 and AGP2 laboratory cycloheximide resistance associations. Distinguished historical L29 from modern RPL29, kept UniProt proteins and S288c taxonomy reference-only, and retained mechanistic and numerical-endpoint limitations. Existing source-owned claims are unchanged; whole-record review remains open.

  40. REVIEWED_RESISTANCE_SUBJECT_CONTEXT 2026-10-13 · codex · LLM-assisted

    Refreshed the shared PHI-base review checksum after one Neurospora subject-context correction; previous decisions, biological fields and activities unchanged.

  41. CURATED_UNIPROT_PROTEIN_EXAMPLES 2026-10-18 · antigravity · LLM-assisted

    Added curated Saccharomyces cerevisiae S288c 60S ribosomal protein uL15 / RPL28 (P02406) UniProtKB protein example on the PRIMARY_LITERATURE eukaryotic 80S ribosome molecular target.

Provenance

Seeded by scripts/seed_from_sources.py from the committed inventories in data/raw/. View the record (YAML).

Explore across X-Mech: MediaIngredientMech (cycloheximide) · CultureMech · NaturalProductMech · PathwayMech · TraitMech