Drug Information

Drug (ID: DG00051) and It's Reported Resistant Information

• Name: Cerulenin
• Synonyms: Helicocerin; Cerulenin, Cephalosporium caerulens; Oxiranecarboxamide, 3-(1-oxo-4,7-nonadienyl)-, (2R-(2-alpha,3-alpha(4E,7E)))-(9CI); (2R,3S)-2,3-Epoxy-4-oxo-7E,10E-dodecadienamide; (2R,3S)-3-((4E,7E)-Nona-4,7-dienoyl)-oxirane-2-carboxylic acid amide; (2R,3S)-3-((4E,7E)-nona-4,7-dienoyl)oxirane-2-carboxamide; (2R,3S)-3-[(4E,7E)-nona-4,7-dienoyl]oxirane-2-carboxamide; (2R,3S)-3-nona-4,7-dienoyloxirane-2-carboxamide; (2R,3S,E,E)-2,3-Epoxy-4-oxo-7,10-dodecadienamide; (2R-(2alpha,3alpha(4E,7E)))-3-(1-Oxonona-4,7-dienyl)oxirane-2-carboxamide; (2S)(3R)-2,3-Epoxy-4-oxo-7,10-dodecadienoylamide; (2S,3R)-2,3-epoxy-4-oxy-7,10-dodecadienoylamide; (2r,3s)-3-(nona-4,7-dienoyl)oxirane-2-carboxamide; 2,3-Epoxy-4-oxo-7,10-dodecadienamide; 2,3-Epoxy-4-oxo-7,10-dodecadienoylamide; 3-(1-Oxo-4,7-nonadienyl)oxiranecarboxamide; 3-[(4E,7E)-nona-4,7-dienoyl]oxirane-2-carboxamide; 3-nona-4,7-dienoyloxirane-2-carboxamide
• Indication:
  In total 1 Indication(s)
  concerning food/fluid intake symptom [ICD-11: MG43]; Approved; [1]
• Target: Fatty acid synthase (FASN); FAS_HUMAN; [1]
• Formula: C12H17NO3
• IsoSMILES: C/C=C/C/C=C/CCC(=O)[C@@H]1[C@@H](O1)C(=O)N
• InChI: 1S/C12H17NO3/c1-2-3-4-5-6-7-8-9(14)10-11(16-10)12(13)15/h2-3,5-6,10-11H,4,7-8H2,1H3,(H2,13,15)/b3-2+,6-5+/t10-,11-/m1/s1
• InChIKey: GVEZIHKRYBHEFX-NQQPLRFYSA-N
• PubChem CID: 5282054
• ChEBI ID: CHEBI:171741
• TTD Drug ID: D03ZFG
• DrugBank ID: DB01034

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Candidosis [ICD-11: 1F23]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs CDR1 (CDR1) [1]

• Sensitive Disease: Recurrent oropharyngeal candidiasis [ICD-11: 1F23.6]
• Molecule Alteration: Deletion mutation; Deleteion
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida albicans strain DSY448; 5476
• Experiment for Molecule Alteration: PCR; Southern blotting analysis; Northern blottling analysis
• Experiment for Drug Resistance: Growth differences between the different C. albicans strains assay
• Mechanism Description: The delta cdr1 mutant was slightly more susceptible than the wild type to nocodazole, cerulenin, and crystal violet but not to amphotericin B, nikkomy- cin Z, flucytosine, or pradimicin.

Key Molecule: Pleiotropic ABC efflux transporter of multiple drugs CDR /Multidrug resistance protein 1 (CDR1/ABCB1) [1]

• Sensitive Disease: Recurrent oropharyngeal candidiasis [ICD-11: 1F23.6]
• Molecule Alteration: Deletion mutation; Deleteion
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Candida tropicalis strain DSY468; 5482
• Experiment for Molecule Alteration: PCR; Southern blotting analysis; Northern blottling analysis
• Experiment for Drug Resistance: Growth differences between the different C. albicans strains assay
• Mechanism Description: The double delta cdr1 and delta ben mutant DSY468 showed increased growth inhibition in plates containing cyclo-heximide and cerulenin compared with the growth of strain CAF2-1 and of the delta ben mutant DSY465. A slight increase in the level of inhibition of DSY468 compared with that of the delta cdr1 mutant DSY448 was observed with cycloheximide, whereas this effect was more severe with cerulenin.

ICD-02: Benign/in-situ/malignant neoplasm

Liver cancer [ICD-11: 2C12]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Fatty acid synthase (FASN) [2]

• Metabolic Type: Lipid metabolism
• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HepG2/C3A cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Huh7 cells; Kidney; Homo sapiens (Human); CVCL_U442
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Importantly, our RNA sequencing analysis disclosed that the amyloid protein precursor (APP) is a crucial downstream effector of FASN in regulating CSC properties. We found that APP plays a crucial role in CSCs' characteristics that can be inhibited by cerulenin.

References

• Ref 1: Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors. Antimicrob Agents Chemother. 1996 Oct;40(10):2300-5. doi: 10.1128/AAC.40.10.2300.
• Ref 2: Fatty acid synthase inhibitor cerulenin hinders liver cancer stem cell properties through FASN/APP axis as novel therapeutic strategies. J Lipid Res. 2024 Nov;65(11):100660.