Cerulenin (T3D2964)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2009-07-21 20:28:13 UTC
Update Date2014-12-24 20:25:54 UTC
Accession NumberT3D2964
Identification
Common NameCerulenin
ClassSmall Molecule
DescriptionCerulenin is an antifungal antibiotic that inhibits sterol and fatty acid biosynthesis. In fatty acid synthesis, reported to bind in equimolar ratio to b-keto-acyl-ACP synthase. In sterol synthesis, inhibits HMG-CoA synthetase activity. It is also shown to inhibit feeding and induce dramatic weight loss in mice. It is found naturally in the Cephalosporium caerulensfungus. [Wikipedia]
Compound Type
  • Antibiotic, Antifungal
  • Antifungal Agent
  • Drug
  • Ether
  • Fatty Acid Synthesis Inhibitor
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(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
Helicocerin
Chemical FormulaC12H17NO3
Average Molecular Mass223.268 g/mol
Monoisotopic Mass223.121 g/mol
CAS Registry Number17397-89-6
IUPAC Name(2R,3S)-3-(nona-4,7-dienoyl)oxirane-2-carboxamide
Traditional Namecerulenin
SMILES[H]\C(C)=C(\[H])C\C([H])=C(/[H])CCC(=O)[C@@]1([H])O[C@@]1([H])C(O)=N
InChI IdentifierInChI=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
InChI KeyInChIKey=GVEZIHKRYBHEFX-NQQPLRFYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as oxirane carboxylic acids and derivatives. Oxirane carboxylic acids and derivatives are compounds containing an oxirane ring bearing a carboxylic acid group (or a derivative thereof).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassEpoxides
Sub ClassOxirane carboxylic acids and derivatives
Direct ParentOxirane carboxylic acids and derivatives
Alternative Parents
Substituents
  • Oxirane carboxylic acid or derivatives
  • Monosaccharide
  • Carboxamide group
  • Ketone
  • Primary carboxylic acid amide
  • Carboxylic acid derivative
  • Dialkyl ether
  • Ether
  • Oxacycle
  • Carbonyl group
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point93.5°C
Boiling PointNot Available
SolubilitySlightly soluble
LogP1.2
Predicted Properties
PropertyValueSource
Water Solubility1.6 g/LALOGPS
logP1.38ALOGPS
logP1.5ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)14.16ChemAxon
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area72.69 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity62.54 m³·mol⁻¹ChemAxon
Polarizability23.9 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-06rf-9600000000-ac88ca6a297eb89d73b42017-08-28View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-05fr-1290000000-202e41a2408ad9df3f622017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4r-8950000000-c0265c2ede42a8a7b9442017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0frf-9100000000-c8d70361d98f08b9775a2017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-4490000000-130e0abcad17614007d82017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0570-9830000000-b6afbfbbfa11b458c4ba2017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-289b3846b10b0578e10f2017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-05fr-6970000000-a192a4a992558941f3f02021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-9400000000-f684bf91e79510c00ed82021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9200000000-91ff9f0cebc2d5a63e302021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00dl-6290000000-dc435b26c818bc2f01342021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9100000000-ac3aa58779f68cf0a7992021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-79c001be721cdc21c3742021-10-11View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityIrreversibly binds to fatty acid synthase, specifically b-ketoacyl-acyl carrier protein synthase (FabH, FabB and FabF condensation enzymes). A number of tumor cells and cell lines have been observed to have highly upregulated expression and activity of fatty acid synthase (FAS). Inhibition of FAS by cerulenin leads to cytotoxicity and apoptosis in human cancer cell lines, an effect believed to be mediated by the accumulation of malonyl-coenzyme A in cells with an upregulated FAS pathway.
MetabolismNot Available
Toxicity ValuesLD50: 547 mg/kg (Oral, Mouse) (3)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor use as a biochemical tool, Cerulenin is shown to cause dramatic weight loss in animals
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overexposure include moderate to severe erythema (redness) and moderate edema (raised skin), nausea, vomiting, and headache.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01034
HMDB IDHMDB15168
PubChem Compound ID5282054
ChEMBL IDCHEMBL45627
ChemSpider ID26530
KEGG IDC12058
UniProt IDNot Available
OMIM ID
ChEBI ID171741
BioCyc IDCPD-6901
CTD IDNot Available
Stitch IDCerulenin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkCerulenin
References
Synthesis Reference

Garfield P. Royer, Craig A. Townsend, “Cerulenin compounds for fatty acid synthesis inhibition.” U.S. Patent US5539132, issued July, 1975.

MSDSLink
General References
  1. Huang P, Zhu S, Lu S, Dai Z, Jin Y: [An experimental study on cerulenin induced apoptosis of human colonic cancer cells]. Zhonghua Bing Li Xue Za Zhi. 2000 Apr;29(2):115-8. [11866903 ]
  2. Straub SG, Yajima H, Komatsu M, Aizawa T, Sharp GW: The effects of cerulenin, an inhibitor of protein acylation, on the two phases of glucose-stimulated insulin secretion. Diabetes. 2002 Feb;51 Suppl 1:S91-5. [11815464 ]
  3. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Fatty acid synthase
General Function:
Poly(a) rna binding
Specific Function:
Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities and an acyl carrier protein.
Gene Name:
FASN
Uniprot ID:
P49327
Molecular Weight:
273424.06 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5013 uMNot AvailableBindingDB 50009248
IC5021.86 uMNot AvailableBindingDB 50009248
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Oskouian B, Saba JD: YAP1 confers resistance to the fatty acid synthase inhibitor cerulenin through the transporter Flr1p in Saccharomyces cerevisiae. Mol Gen Genet. 1999 Mar;261(2):346-53. [10102370 ]
  3. Li JN, Gorospe M, Chrest FJ, Kumaravel TS, Evans MK, Han WF, Pizer ES: Pharmacological inhibition of fatty acid synthase activity produces both cytostatic and cytotoxic effects modulated by p53. Cancer Res. 2001 Feb 15;61(4):1493-9. [11245456 ]
  4. Parrish NM, Kuhajda FP, Heine HS, Bishai WR, Dick JD: Antimycobacterial activity of cerulenin and its effects on lipid biosynthesis. J Antimicrob Chemother. 1999 Feb;43(2):219-26. [11252327 ]
  5. Zou Z, DiRusso CC, Ctrnacta V, Black PN: Fatty acid transport in Saccharomyces cerevisiae. Directed mutagenesis of FAT1 distinguishes the biochemical activities associated with Fat1p. J Biol Chem. 2002 Aug 23;277(34):31062-71. Epub 2002 Jun 6. [12052836 ]
  6. Heiligtag SJ, Bredehorst R, David KA: Key role of mitochondria in cerulenin-mediated apoptosis. Cell Death Differ. 2002 Sep;9(9):1017-25. [12181752 ]
  7. Na M, Jang J, Min BS, Lee SJ, Lee MS, Kim BY, Oh WK, Ahn JS: Fatty acid synthase inhibitory activity of acylphloroglucinols isolated from Dryopteris crassirhizoma. Bioorg Med Chem Lett. 2006 Sep 15;16(18):4738-42. Epub 2006 Jul 25. [16870425 ]
  8. Abramson HN: The lipogenesis pathway as a cancer target. J Med Chem. 2011 Aug 25;54(16):5615-38. doi: 10.1021/jm2005805. Epub 2011 Aug 3. [21726077 ]