DT-Web

DB01034 - Cerulenin


Identification
Name Cerulenin
Accession Number DB01034 (APRD00703)
Type small molecule
Description Cerulenin 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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 223.2683
Groups approved
Monoisotopic Weight 223.120843415
Pharmacology
Indication For use as a biochemical tool, Cerulenin is shown to cause dramatic weight loss in animals
Mechanism of action Irreversibly 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.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Oral, 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
  • Bacteria
  • Fungi
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


3-oxoacyl-[acyl-carrier-protein] synthase 1
Name 3-oxoacyl-[acyl-carrier-protein] synthase 1
Gene Name fabB
Pharmacological action yes
Actions inhibitor
References
  • 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
  • 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
  • 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
  • Heath RJ, Rock CO: Fatty acid biosynthesis as a target for novel antibacterials. Curr Opin Investig Drugs. 2004 Feb;5(2):146-53. - Pubmed
  • 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
  • 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
  • Heath RJ, White SW, Rock CO: Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res. 2001 Nov;40(6):467-97. - Pubmed
DTHybrid score 1.4818
3-oxoacyl-[acyl-carrier-protein] synthase 2
Name 3-oxoacyl-[acyl-carrier-protein] synthase 2
Gene Name fabF
Pharmacological action yes
Actions inhibitor
References
  • 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
  • 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
  • Heath RJ, Rock CO: Fatty acid biosynthesis as a target for novel antibacterials. Curr Opin Investig Drugs. 2004 Feb;5(2):146-53. - Pubmed
  • 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
  • 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
  • Heath RJ, White SW, Rock CO: Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res. 2001 Nov;40(6):467-97. - Pubmed
  • 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
DTHybrid score 1.546
3-oxoacyl-[acyl-carrier-protein] synthase 3
Name 3-oxoacyl-[acyl-carrier-protein] synthase 3
Gene Name fabH
Pharmacological action yes
Actions inhibitor
References
  • 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
  • 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
  • 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
  • Heath RJ, Rock CO: Fatty acid biosynthesis as a target for novel antibacterials. Curr Opin Investig Drugs. 2004 Feb;5(2):146-53. - Pubmed
  • 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
  • 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
  • Heath RJ, White SW, Rock CO: Lipid biosynthesis as a target for antibacterial agents. Prog Lipid Res. 2001 Nov;40(6):467-97. - Pubmed
DTHybrid score 1.078
Fatty acid synthase
Name Fatty acid synthase
Gene Name FASN
Pharmacological action yes
Actions inhibitor
References
  • 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
  • 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
  • Heiligtag SJ, Bredehorst R, David KA: Key role of mitochondria in cerulenin-mediated apoptosis. Cell Death Differ. 2002 Sep;9(9):1017-25. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • 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. - Pubmed
  • 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
  • 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
DTHybrid score 0.5844

Predictions


Id Partner name Gene Name Score
6860 3-oxoacyl-[acyl-carrier-protein] synthase 1 kasA 1.4818
3138 3-oxoacyl-[acyl-carrier-protein] synthase 3 fabH 1.078
4568 3-oxoacyl-[acyl-carrier-protein] synthase 3 fabH 1.078
6370 3-oxoacyl-[acyl-carrier-protein] synthase 3 fabH 1.078
6116 Gastric triacylglycerol lipase LIPF 0.1227
4589 3-hydroxy-3-methylglutaryl CoA synthase mvaS 0.1041
754 Pancreatic triacylglycerol lipase PNLIP 0.1002
2596 Acetyl-CoA acetyltransferase phbA 0.0898
723 Cytosolic phospholipase A2 PLA2G4A 0.0819
3686 Acyl-CoA thioesterase I precursor tesA 0.0589
6508 Putative uncharacterized protein srtB 0.0565
6543 Putative uncharacterized protein tcp14 0.0565
6615 Putative uncharacterized protein MT0785 0.0565
6623 Putative uncharacterized protein Not Available 0.0565
6806 Putative uncharacterized protein AGR_C_2535 0.0565
6813 Putative uncharacterized protein SAV4671 0.0565
6815 Putative uncharacterized protein AFE_1514 0.0565
6819 Putative uncharacterized protein RUMGNA_03254 0.0565
6825 Putative uncharacterized protein CV_3270 0.0565
4161 Furin FURIN 0.0564
6541 Peptostreptococcal albumin-binding protein pab 0.0491
3382 Glycolipid transfer protein GLTP 0.0396
4512 Cytochrome P450 3A4 CYP3A4 0.0341
5366 Sugar-phosphate isomerase TM_1080 0.0253
2688 Peptide deformylase def 0.0253
2708 Peptide deformylase def 0.0253
3004 Peptide deformylase def 0.0253
4337 Peptide deformylase def 0.0253
4338 Peptide deformylase def 0.0253
5368 Peptide deformylase def 0.0253
5371 Peptide deformylase def 0.0253
6375 Peptide deformylase def 0.0253
6378 Peptide deformylase def 0.0253
6379 Peptide deformylase def 0.0253
6776 Peptide deformylase def 0.0253
6900 Peptide deformylase def 0.0253
5365 Metallo beta-lactamase blaVIM-2 0.0252
5369 Golgi-associated plant pathogenesis-related protein 1 GLIPR2 0.0252
4699 Methylaspartate ammonia-lyase Not Available 0.0252
5367 Peroxiredoxin prx 0.0252
1024 Solute carrier family 22 member 11 SLC22A11 0.0228
3596 Deoxynucleotide monophosphate kinase 1 0.022
3858 Cathepsin L CTSL1 0.022
6142 Solute carrier family 22 member 8 SLC22A8 0.0203
3105 M-phase inducer phosphatase 2 CDC25B 0.0202
2664 S-ribosylhomocysteine lyase luxS 0.0192
2725 S-ribosylhomocysteine lyase luxS 0.0192
2385 Penicillin acylase Not Available 0.0181
1729 Solute carrier family 22 member 6 SLC22A6 0.0181
587 Serum albumin ALB 0.0156
687 Tyrosine-protein phosphatase non-receptor type 1 PTPN1 0.0113
4564 YvbK protein yvbK 0.0093
4576 Aac(6')-Ii protein aac(6')-Ii 0.0093
2528 Fatty acid metabolism regulator protein fadR 0.0093
6740 Fatty acid metabolism regulator protein fadR 0.0093
4579 Serine acetyltransferase cysE 0.0093
6807 Serine acetyltransferase cysE 0.0093
4567 Putative acyl-CoA thioester hydrolase HI0827 HI_0827 0.0093
4577 4'-phosphopantetheinyl transferase sfp sfp 0.0093
4566 Acyl-CoA hydrolase BC_2038 0.0093
4572 Acyl-CoA hydrolase BH0798 0.0093
4037 Hypothetical protein GPX1 0.0093
4297 Hypothetical protein SP_1951 0.0093
4521 Hypothetical protein BC_2969 0.0093
4540 Hypothetical protein TM_1070 0.0093
4555 Hypothetical protein MT1739 0.0093
4569 Hypothetical protein mshD 0.0093
4578 Hypothetical protein PA3270 0.0093
4747 Hypothetical protein PA3967 0.0093
5177 Hypothetical protein TM_0096 0.0093
5194 Hypothetical protein PA1204 0.0093
5240 Hypothetical protein Rv2991 0.0093
5370 Hypothetical protein TM_1158 0.0093
5710 Hypothetical protein Tb927.5.1360 0.0093
3560 Gentamicin 3'-acetyltransferase aacC1 0.0081
4565 Aminoglycoside 6'-N-acetyltransferase aac(6')-Iy 0.0081
3489 Acetyl-coenzyme A synthetase acs 0.0081
4574 PROBABLE NAPHTHOATE SYNTHASE MENB menB 0.0081
2396 Formyl-coenzyme A transferase frc 0.0081
3457 Formyl-coenzyme A transferase frc 0.0081
4563 Acetyl transferase rimL 0.0081
3024 Crotonobetainyl-CoA:carnitine CoA-transferase caiB 0.0081
3317 Holo-[acyl-carrier-protein] synthase acpS 0.0081
4381 Holo-[acyl-carrier-protein] synthase acpS 0.0081
3125 Protease synthase and sporulation negative regulatory protein PAI 1 paiA 0.0081
2409 Acetyl-CoA acetyltransferase, cytosolic ACAT2 0.008
3729 Citrate synthase gltA 0.008
4575 Citrate synthase cit 0.008
4580 Citrate synthase gltA 0.008
2285 Streptogramin A acetyltransferase vatD 0.0075
3199 Phosphopantetheine adenylyltransferase coaD 0.0075
3543 Phosphopantetheine adenylyltransferase coaD 0.0075
3567 Phosphopantetheine adenylyltransferase coaD 0.0075
5289 Phosphopantetheine adenylyltransferase coaD 0.0075
2377 Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex Not Available 0.0074
2560 Galactoside O-acetyltransferase lacA 0.0074
3178 Formate acetyltransferase 1 pflB 0.0074
4573 Histone acetyltransferase PCAF KAT2B 0.0074
3697 Bifunctional protein glmU [Includes: UDP-N-acetylglucosamine pyrophosphorylase glmU 0.0074
2248 Malate synthase G glcB 0.0074
3190 Malate synthase G glcB 0.0074
2371 Pantothenate kinase coaA 0.0072
4404 FcbC1 protein fcbC 0.007
2376 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase dapD 0.0067
551 Carnitine O-acetyltransferase CRAT 0.0066
4388 Aminoglycoside 2'-N-acetyltransferase aac 0.0058
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0045
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0045
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