Cerulenin

{{chembox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 401951338

| ImageFile=Cerulenin.svg

| ImageSize=280

| PIN=(2R,3S)-3-[(4E,7E)-Nona-4,7-dienoyl]oxirane-2-carboxamide

| OtherNames=

|Section1={{Chembox Identifiers

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 4445281

| 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

| InChIKey = GVEZIHKRYBHEFX-NQQPLRFYBP

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = GVEZIHKRYBHEFX-NQQPLRFYSA-N

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo=17397-89-6

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = MF286Y830Q

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG=C12058

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 45627

| PubChem=5282054

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| DrugBank = DB01034

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 171741

| SMILES = O=C(CC/C=C/C/C=C/C)[C@H]1O[C@H]1C(=O)N

}}

|Section2={{Chembox Properties

| C=12 | H=17 | N=1 | O=3

| MolarMass = 223.2695

| Appearance =

| Density = 1.135 g/mL

| MeltingPt=

| BoilingPtC= 456.14

| Solubility=

}}

|Section3={{Chembox Hazards

| MainHazards=

| FlashPt=

| AutoignitionPt =

}}

}}

Cerulenin is an antifungal antibiotic that inhibits fatty acid and steroid biosynthesis. It was the first natural product antibiotic known to inhibit lipid synthesis.{{cite journal | last1=Volpe | first1=J J | last2=Vagelos | first2=P R | title=Mechanisms and regulation of biosynthesis of saturated fatty acids. | journal=Physiological Reviews | publisher=American Physiological Society | volume=56 | issue=2 | year=1976 | issn=0031-9333 | doi=10.1152/physrev.1976.56.2.339 | pages=339–417| pmid=6981 }} 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.{{cite journal |vauthors=Straub SG, Yajima H, Komatsu M, Aizawa T, Sharp GW |title=The effects of cerulenin, an inhibitor of protein acylation, on the two phases of glucose-stimulated insulin secretion |journal=Diabetes |volume=51 Suppl 1 |issue= 90001|pages=S91–5 |date=February 2002 |pmid=11815464 |doi= 10.2337/diabetes.51.2007.S91|url=http://diabetes.diabetesjournals.org/cgi/content/full/51/suppl_1/S91|doi-access=free }} These two behaviors may increase the availability of energy in the form of ATP, perhaps sensed by AMPK, in the hypothalamus.Reviewed in {{cite journal |vauthors=Ronnett GV, Kleman AM, Kim EK, Landree LE, Tu Y |title=Fatty acid metabolism, the central nervous system, and feeding |journal=Obesity (Silver Spring) |volume=14 |pages=201S–207S |date=August 2006 |issue=Suppl 5 |pmid=17021367 |doi=10.1038/oby.2006.309 |doi-access=free }}

In sterol synthesis, cerulenin inhibits HMG-CoA synthetase activity.{{cite journal |vauthors=Ohno T, Awaya J, Kesado T, Nomura S, Omura S |title=Mechanism of Action of CM-55, a Synthetic Analogue of the Antilipogenic Antibiotic Cerulenin |journal=Antimicrob. Agents Chemother. |volume=6 |issue=4 |pages=387–92 |date=October 1974 |pmid=4157441 |doi= 10.1128/aac.6.4.387|url= |pmc=444657}} It was also reported that cerulenin specifically inhibited fatty acid biosynthesis in Saccharomyces cerevisiae without having an effect on sterol formation. But in general conclusion, cerulenin has inhibitory effects on sterol synthesis.{{cn|date=June 2022}}

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.{{cite journal |vauthors=Menendez JA, Vellon L, Mehmi I |title=Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue=29 |pages=10715–20 |date=July 2004 |pmid=15235125 |doi=10.1073/pnas.0403390101 |pmc=490000|display-authors=etal|doi-access=free |bibcode=2004PNAS..10110715M }} Antiproliferative and pro-apoptotic effects have been shown in colon cells as well.{{cite journal |vauthors=Huang P, Zhu S, Lu S, Dai Z, Jin Y |title=[An experimental study on cerulenin induced apoptosis of human colonic cancer cells] |language=zh |journal=Zhonghua Bing Li Xue Za Zhi |volume=29 |issue=2 |pages=115–8 |date=April 2000 |pmid=11866903 }} 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.{{cite journal |vauthors=Ghosh MK, Amudha R, Jayachandran S, Sakthivel N |title=Detection and quantification of phytotoxic metabolites of Sarocladium oryzae in sheath rot-infected grains of rice |journal=Lett. Appl. Microbiol. |volume=34 |issue=6 |pages=398–401 |year=2002 |pmid=12028418 |doi= 10.1046/j.1472-765X.2002.01111.x|doi-access=free }} It is found naturally in the industrial strain Cephalosporium caerulens (Sarocladium oryzae, the sheath rot pathogen of rice).{{cn|date=December 2022}}