Cerulenin

Cerulenin
Names
	Preferred IUPAC name (2R,3S)-3-[(4E,7E)-Nona-4,7-dienoyl]oxirane-2-carboxamide
Identifiers
CAS Number	17397-89-6 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:171741 ;
ChEMBL	ChEMBL45627 ;
ChemSpider	4445281 ;
DrugBank	DB01034 ;
ECHA InfoCard	100.037.643
KEGG	C12058 ;
PubChem CID	5282054;
UNII	MF286Y830Q ;
CompTox Dashboard (EPA)	DTXSID2040995 ;
	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 Key: GVEZIHKRYBHEFX-NQQPLRFYSA-N ; InChI=1/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 Key: GVEZIHKRYBHEFX-NQQPLRFYBP;
	SMILES O=C(CC/C=C/C/C=C/C)[C@H]1O[C@H]1C(=O)N;
Properties
Chemical formula	C12H17NO3
Molar mass	223.2695
Density	1.135 g/mL
Boiling point	456.14 °C (853.05 °F; 729.29 K)
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Cerulenin is an antifungal antibiotic that inhibits fatty acid and steroid biosynthesis. It was the first natural product antibiotic known to inhibit lipid synthesis.^[1] In fatty acid synthesis, it has been reported to bind in equimolar ratio to b-keto-acyl-ACP synthase, one of the seven moieties of fatty acid synthase, blocking the interaction of malonyl-CoA. It also has the related activity of stimulating fatty acid oxidation through the activation of CPT1, another enzyme normally inhibited by malonyl-CoA. Inhibition involves covalent thioacylation that permanently inactivates the enzymes.^[2] These two behaviors may increase the availability of energy in the form of ATP, perhaps sensed by AMPK, in the hypothalamus.^[3]

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In sterol synthesis, cerulenin inhibits HMG-CoA synthetase activity.^[4] It was also reported that cerulenin specifically inhibited fatty acid biosynthesis in Saccharomyces cerevisiae without having an effect on sterol formation.^[4] But in general conclusion, cerulenin has inhibitory effects on sterol synthesis.^{[citation needed]}

Cerulenin causes a dose-dependent decrease in HER2/neu protein levels in breast cancer cells, from 14% at 1.25 to 78% at 10 milligrams per liter, and targeting of fatty acid synthase by related drugs has been suggested as a possible treatment.^[5] Antiproliferative and pro-apoptotic effects have been shown in colon cells as well.^[6] At an intraperitoneal dose of 30 milligrams per kilogram, it has been shown to inhibit feeding and induce dramatic weight loss in mice by a mechanism similar to, but independent or downstream of, leptin signaling.^[7] It is found naturally in the industrial strain Cephalosporium caerulens (Sarocladium oryzae, the sheath rot pathogen of rice).^{[citation needed]}

Satoshi Ōmura

[1]
Volpe, J J; Vagelos, P R (1976). "Mechanisms and regulation of biosynthesis of saturated fatty acids". Physiological Reviews. 56 (2). American Physiological Society: 339–417. doi:10.1152/physrev.1976.56.2.339. ISSN 0031-9333. PMID 6981.
[2]
Straub SG, Yajima H, Komatsu M, Aizawa T, Sharp GW (February 2002). "The effects of cerulenin, an inhibitor of protein acylation, on the two phases of glucose-stimulated insulin secretion". Diabetes. 51 Suppl 1 (90001): S91–5. doi:10.2337/diabetes.51.2007.S91. PMID 11815464.
[3]
Reviewed in Ronnett GV, Kleman AM, Kim EK, Landree LE, Tu Y (August 2006). "Fatty acid metabolism, the central nervous system, and feeding". Obesity (Silver Spring). 14 (Suppl 5): 201S – 207S. doi:10.1038/oby.2006.309. PMID 17021367.
[4]
Ohno T, Awaya J, Kesado T, Nomura S, Omura S (October 1974). "Mechanism of Action of CM-55, a Synthetic Analogue of the Antilipogenic Antibiotic Cerulenin". Antimicrob. Agents Chemother. 6 (4): 387–92. doi:10.1128/aac.6.4.387. PMC 444657. PMID 4157441.
[5]
Menendez JA, Vellon L, Mehmi I, et al. (July 2004). "Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells". Proc. Natl. Acad. Sci. U.S.A. 101 (29): 10715–20. Bibcode:2004PNAS..10110715M. doi:10.1073/pnas.0403390101. PMC 490000. PMID 15235125.
[6]
Huang P, Zhu S, Lu S, Dai Z, Jin Y (April 2000). "[An experimental study on cerulenin induced apoptosis of human colonic cancer cells]". Zhonghua Bing Li Xue Za Zhi (in Chinese). 29 (2): 115–8. PMID 11866903.
[7]
Ghosh MK, Amudha R, Jayachandran S, Sakthivel N (2002). "Detection and quantification of phytotoxic metabolites of Sarocladium oryzae in sheath rot-infected grains of rice". Lett. Appl. Microbiol. 34 (6): 398–401. doi:10.1046/j.1472-765X.2002.01111.x. PMID 12028418.

Cerulenin from Fermentek

[Volpe_Vagelos_1976_pp._339–417-1] [1]
Volpe, J J; Vagelos, P R (1976). "Mechanisms and regulation of biosynthesis of saturated fatty acids". Physiological Reviews. 56 (2). American Physiological Society: 339–417. doi:10.1152/physrev.1976.56.2.339. ISSN 0031-9333. PMID 6981.

[2] [2]
Straub SG, Yajima H, Komatsu M, Aizawa T, Sharp GW (February 2002). "The effects of cerulenin, an inhibitor of protein acylation, on the two phases of glucose-stimulated insulin secretion". Diabetes. 51 Suppl 1 (90001): S91–5. doi:10.2337/diabetes.51.2007.S91. PMID 11815464.

[3] [3]
Reviewed in Ronnett GV, Kleman AM, Kim EK, Landree LE, Tu Y (August 2006). "Fatty acid metabolism, the central nervous system, and feeding". Obesity (Silver Spring). 14 (Suppl 5): 201S – 207S. doi:10.1038/oby.2006.309. PMID 17021367.

[Ohno-4] [4]
Ohno T, Awaya J, Kesado T, Nomura S, Omura S (October 1974). "Mechanism of Action of CM-55, a Synthetic Analogue of the Antilipogenic Antibiotic Cerulenin". Antimicrob. Agents Chemother. 6 (4): 387–92. doi:10.1128/aac.6.4.387. PMC 444657. PMID 4157441.

[5] [5]
Menendez JA, Vellon L, Mehmi I, et al. (July 2004). "Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells". Proc. Natl. Acad. Sci. U.S.A. 101 (29): 10715–20. Bibcode:2004PNAS..10110715M. doi:10.1073/pnas.0403390101. PMC 490000. PMID 15235125.

[6] [6]
Huang P, Zhu S, Lu S, Dai Z, Jin Y (April 2000). "[An experimental study on cerulenin induced apoptosis of human colonic cancer cells]". Zhonghua Bing Li Xue Za Zhi (in Chinese). 29 (2): 115–8. PMID 11866903.

[7] [7]
Ghosh MK, Amudha R, Jayachandran S, Sakthivel N (2002). "Detection and quantification of phytotoxic metabolites of Sarocladium oryzae in sheath rot-infected grains of rice". Lett. Appl. Microbiol. 34 (6): 398–401. doi:10.1046/j.1472-765X.2002.01111.x. PMID 12028418.

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Cerulenin

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