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Identification
NameCerulenin
Accession NumberDB01034  (APRD00703)
TypeSmall Molecule
GroupsApproved
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]
Structure
Thumb
Synonyms
(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
Cerulenin
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
HelicocerinNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIMF286Y830Q
CAS number17397-89-6
WeightAverage: 223.2683
Monoisotopic: 223.120843415
Chemical FormulaC12H17NO3
InChI KeyInChIKey=GVEZIHKRYBHEFX-NQQPLRFYSA-N
InChI
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
IUPAC Name
(2R,3S)-3-(nona-4,7-dienoyl)oxirane-2-carboxamide
SMILES
CC=CCC=CCCC(=O)[[email protected]]1O[[email protected]]1C(N)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as oxirane carboxylic acids and derivatives. These 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
  • Gamma-aminoketone
  • Primary carboxylic acid amide
  • Ketone
  • Carboxamide group
  • Oxacycle
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor use as a biochemical tool, Cerulenin is shown to cause dramatic weight loss in animals
PharmacodynamicsCerulenin is an antifungal antibiotic isolated from Cephalosporium caerulens. It interrupts fungal growth by inhibiting the biosynthesis of sterols and fatty acids (inhibits bacterial fatty acid synthesis). It also inhibits HMG-CoA synthetase activity. Cerulenin produces metabolic effects similar to effects of leptin, but through mechanisms that are independent of, or down-stream from, both leptin and melanocortin receptors.
Mechanism of actionIrreversibly 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityOral, mouse LD50: 547 mg/kg. Symptoms of overexposure include moderate to severe erythema (redness) and moderate edema (raised skin), nausea, vomiting, and headache.
Affected organisms
  • Humans and other mammals
  • Fungi
  • Mycobacterium tuberculosis
  • Bacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9957
Blood Brain Barrier+0.9711
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.7289
P-glycoprotein inhibitor INon-inhibitor0.5928
P-glycoprotein inhibitor IINon-inhibitor0.8271
Renal organic cation transporterNon-inhibitor0.9197
CYP450 2C9 substrateNon-substrate0.8017
CYP450 2D6 substrateNon-substrate0.8147
CYP450 3A4 substrateNon-substrate0.6391
CYP450 1A2 substrateNon-inhibitor0.6305
CYP450 2C9 inhibitorNon-inhibitor0.7838
CYP450 2D6 inhibitorNon-inhibitor0.9346
CYP450 2C19 inhibitorNon-inhibitor0.64
CYP450 3A4 inhibitorNon-inhibitor0.9438
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8871
Ames testAMES toxic0.6488
CarcinogenicityNon-carcinogens0.8611
BiodegradationNot ready biodegradable0.8853
Rat acute toxicity2.0415 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9659
hERG inhibition (predictor II)Non-inhibitor0.9698
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point93.5 °CPhysProp
water solubilitySlightly solubleNot Available
logP1.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.6 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity62.54 m3·mol-1ChemAxon
Polarizability23.9 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

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

US5539132
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. [PubMed: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. [PubMed:11815464 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (25.4 KB)
Interactions
Drug Interactions
Drug
AmlodipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Amlodipine.
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Cerulenin.
AmrinoneThe risk or severity of adverse effects can be increased when Cerulenin is combined with Amrinone.
AzelnidipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Azelnidipine.
AzimilideThe risk or severity of adverse effects can be increased when Cerulenin is combined with Azimilide.
BarnidipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Barnidipine.
BenidipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Benidipine.
BepridilThe risk or severity of adverse effects can be increased when Cerulenin is combined with Bepridil.
BuspironeThe metabolism of Buspirone can be decreased when combined with Cerulenin.
BusulfanThe serum concentration of Busulfan can be increased when it is combined with Cerulenin.
CilnidipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Cilnidipine.
CinnarizineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Cinnarizine.
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Cerulenin.
ConivaptanThe metabolism of Conivaptan can be decreased when combined with Cerulenin.
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Cerulenin.
DarodipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Darodipine.
DidanosineDidanosine can cause a decrease in the absorption of Cerulenin resulting in a reduced serum concentration and potentially a decrease in efficacy.
DiltiazemThe risk or severity of adverse effects can be increased when Cerulenin is combined with Diltiazem.
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Cerulenin.
DofetilideThe metabolism of Dofetilide can be decreased when combined with Cerulenin.
DotarizineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Dotarizine.
EfonidipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Efonidipine.
EperisoneThe risk or severity of adverse effects can be increased when Cerulenin is combined with Eperisone.
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Cerulenin.
FelodipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Felodipine.
FendilineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Fendiline.
FlunarizineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Flunarizine.
FosphenytoinThe serum concentration of Cerulenin can be decreased when it is combined with Fosphenytoin.
GabapentinThe risk or severity of adverse effects can be increased when Cerulenin is combined with Gabapentin.
IsradipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Isradipine.
LacidipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Lacidipine.
LamotrigineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Lamotrigine.
LercanidipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Lercanidipine.
LosartanThe metabolism of Losartan can be decreased when combined with Cerulenin.
Magnesium SulfateThe risk or severity of adverse effects can be increased when Cerulenin is combined with Magnesium Sulfate.
ManidipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Manidipine.
MibefradilThe risk or severity of adverse effects can be increased when Cerulenin is combined with Mibefradil.
NicardipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Nicardipine.
NifedipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Nifedipine.
NiguldipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Niguldipine.
NiludipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Niludipine.
NilvadipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Nilvadipine.
NimesulideThe risk or severity of adverse effects can be increased when Cerulenin is combined with Nimesulide.
NimodipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Nimodipine.
NisoldipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Nisoldipine.
NitrendipineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Nitrendipine.
PerhexilineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Perhexiline.
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Cerulenin.
PimozideCerulenin may increase the arrhythmogenic activities of Pimozide.
PinaveriumThe risk or severity of adverse effects can be increased when Cerulenin is combined with Pinaverium.
PregabalinThe risk or severity of adverse effects can be increased when Cerulenin is combined with Pregabalin.
PrenylamineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Prenylamine.
ProgesteroneThe therapeutic efficacy of Progesterone can be decreased when used in combination with Cerulenin.
QuinidineThe metabolism of Quinidine can be decreased when combined with Cerulenin.
RanolazineThe metabolism of Ranolazine can be decreased when combined with Cerulenin.
RisedronateThe risk or severity of adverse effects can be increased when Cerulenin is combined with Risedronate.
SolifenacinThe metabolism of Solifenacin can be decreased when combined with Cerulenin.
SucralfateSucralfate can cause a decrease in the absorption of Cerulenin resulting in a reduced serum concentration and potentially a decrease in efficacy.
SunitinibThe metabolism of Sunitinib can be decreased when combined with Cerulenin.
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Cerulenin.
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Cerulenin is combined with Tolfenamic Acid.
TranilastThe risk or severity of adverse effects can be increased when Cerulenin is combined with Tranilast.
VerapamilThe risk or severity of adverse effects can be increased when Cerulenin is combined with Verapamil.
XylometazolineThe risk or severity of adverse effects can be increased when Cerulenin is combined with Xylometazoline.
ZiconotideThe risk or severity of adverse effects can be increased when Cerulenin is combined with Ziconotide.
ZolpidemThe serum concentration of Zolpidem can be increased when it is combined with Cerulenin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
3-oxoacyl-[acyl-carrier-protein] synthase activity
Specific Function:
Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Specific for elongation from C-10 to unsaturated C-16 and C-18 fatty acids.
Gene Name:
fabB
Uniprot ID:
P0A953
Molecular Weight:
42612.995 Da
References
  1. Kauppinen S, Siggaard-Andersen M, von Wettstein-Knowles P: beta-Ketoacyl-ACP synthase I of Escherichia coli: nucleotide sequence of the fabB gene and identification of the cerulenin binding residue. Carlsberg Res Commun. 1988;53(6):357-70. [PubMed:3076376 ]
  2. Price AC, Choi KH, Heath RJ, Li Z, White SW, Rock CO: Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism. J Biol Chem. 2001 Mar 2;276(9):6551-9. Epub 2000 Oct 24. [PubMed:11050088 ]
  3. Slabaugh MB, Leonard JM, Knapp SJ: Condensing enzymes from Cuphea wrightii associated with medium chain fatty acid biosynthesis. Plant J. 1998 Mar;13(5):611-20. [PubMed:9681003 ]
  4. Heath RJ, Rock CO: Fatty acid biosynthesis as a target for novel antibacterials. Curr Opin Investig Drugs. 2004 Feb;5(2):146-53. [PubMed:15043388 ]
  5. Khandekar SS, Daines RA, Lonsdale JT: Bacterial beta-ketoacyl-acyl carrier protein synthases as targets for antibacterial agents. Curr Protein Pept Sci. 2003 Feb;4(1):21-9. [PubMed:12570782 ]
  6. Omura S: The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis. Bacteriol Rev. 1976 Sep;40(3):681-97. [PubMed:791237 ]
  7. Heath RJ, White SW, Rock CO: Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res. 2001 Nov;40(6):467-97. [PubMed:11591436 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Beta-ketoacyl-acyl-carrier-protein synthase ii activity
Specific Function:
Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Has a preference for short chain acid substrates and may function to supply the octanoic substrates for lipoic acid biosynthesis.
Gene Name:
fabF
Uniprot ID:
P0AAI5
Molecular Weight:
43045.39 Da
References
  1. Heath RJ, White SW, Rock CO: Inhibitors of fatty acid synthesis as antimicrobial chemotherapeutics. Appl Microbiol Biotechnol. 2002 May;58(6):695-703. Epub 2002 Mar 7. [PubMed:12021787 ]
  2. Schujman GE, Choi KH, Altabe S, Rock CO, de Mendoza D: Response of Bacillus subtilis to cerulenin and acquisition of resistance. J Bacteriol. 2001 May;183(10):3032-40. [PubMed:11325930 ]
  3. Heath RJ, Rock CO: Fatty acid biosynthesis as a target for novel antibacterials. Curr Opin Investig Drugs. 2004 Feb;5(2):146-53. [PubMed:15043388 ]
  4. Khandekar SS, Daines RA, Lonsdale JT: Bacterial beta-ketoacyl-acyl carrier protein synthases as targets for antibacterial agents. Curr Protein Pept Sci. 2003 Feb;4(1):21-9. [PubMed:12570782 ]
  5. Omura S: The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis. Bacteriol Rev. 1976 Sep;40(3):681-97. [PubMed:791237 ]
  6. Heath RJ, White SW, Rock CO: Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res. 2001 Nov;40(6):467-97. [PubMed:11591436 ]
  7. Price AC, Choi KH, Heath RJ, Li Z, White SW, Rock CO: Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism. J Biol Chem. 2001 Mar 2;276(9):6551-9. Epub 2000 Oct 24. [PubMed:11050088 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Beta-ketoacyl-acyl-carrier-protein synthase iii activity
Specific Function:
Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Has some substrate specificit...
Gene Name:
fabH
Uniprot ID:
P0A6R0
Molecular Weight:
33514.78 Da
References
  1. Young K, Jayasuriya H, Ondeyka JG, Herath K, Zhang C, Kodali S, Galgoci A, Painter R, Brown-Driver V, Yamamoto R, Silver LL, Zheng Y, Ventura JI, Sigmund J, Ha S, Basilio A, Vicente F, Tormo JR, Pelaez F, Youngman P, Cully D, Barrett JF, Schmatz D, Singh SB, Wang J: Discovery of FabH/FabF inhibitors from natural products. Antimicrob Agents Chemother. 2006 Feb;50(2):519-26. [PubMed:16436705 ]
  2. Heath RJ, White SW, Rock CO: Inhibitors of fatty acid synthesis as antimicrobial chemotherapeutics. Appl Microbiol Biotechnol. 2002 May;58(6):695-703. Epub 2002 Mar 7. [PubMed:12021787 ]
  3. Price AC, Choi KH, Heath RJ, Li Z, White SW, Rock CO: Inhibition of beta-ketoacyl-acyl carrier protein synthases by thiolactomycin and cerulenin. Structure and mechanism. J Biol Chem. 2001 Mar 2;276(9):6551-9. Epub 2000 Oct 24. [PubMed:11050088 ]
  4. Heath RJ, Rock CO: Fatty acid biosynthesis as a target for novel antibacterials. Curr Opin Investig Drugs. 2004 Feb;5(2):146-53. [PubMed:15043388 ]
  5. Khandekar SS, Daines RA, Lonsdale JT: Bacterial beta-ketoacyl-acyl carrier protein synthases as targets for antibacterial agents. Curr Protein Pept Sci. 2003 Feb;4(1):21-9. [PubMed:12570782 ]
  6. Omura S: The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis. Bacteriol Rev. 1976 Sep;40(3):681-97. [PubMed:791237 ]
  7. Heath RJ, White SW, Rock CO: Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res. 2001 Nov;40(6):467-97. [PubMed:11591436 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
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
References
  1. 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. [PubMed:10102370 ]
  2. 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. [PubMed:11245456 ]
  3. Heiligtag SJ, Bredehorst R, David KA: Key role of mitochondria in cerulenin-mediated apoptosis. Cell Death Differ. 2002 Sep;9(9):1017-25. [PubMed:12181752 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  5. Flavin R, Peluso S, Nguyen PL, Loda M: Fatty acid synthase as a potential therapeutic target in cancer. Future Oncol. 2010 Apr;6(4):551-62. doi: 10.2217/fon.10.11. [PubMed:20373869 ]
  6. Lupu R, Menendez JA: Pharmacological inhibitors of Fatty Acid Synthase (FASN)--catalyzed endogenous fatty acid biogenesis: a new family of anti-cancer agents? Curr Pharm Biotechnol. 2006 Dec;7(6):483-93. [PubMed:17168665 ]
  7. Ronnett GV, Kim EK, Landree LE, Tu Y: Fatty acid metabolism as a target for obesity treatment. Physiol Behav. 2005 May 19;85(1):25-35. [PubMed:15878185 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23