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{{Short description|Chemical compound}}
{{Drugbox
{{Infobox drug
⚫ | verifiedrevid = 400340989
| Watchedfields = changed
⚫ | IUPAC_name = phenanthren-3-yl] (Z)-octadec-9-enoate
⚫ | verifiedrevid = 447583844
⚫ | IUPAC_name = phenanthren-3-yl] (''Z'')-octadec-9-enoate
| image = Oleoylestrone.png | image = Oleoylestrone.png
| width = 240 | width = 250
| image2 = Oléoyl-estrone_3D.png


<!--Clinical data--> <!--Clinical data-->
| tradename = | tradename =
| licence_EU = | licence_EU =
| licence_US = | licence_US =
| pregnancy_AU = | pregnancy_AU =
| pregnancy_US = | pregnancy_US =
| legal_UK = | legal_UK =
| legal_US = | legal_US =
| routes_of_administration = | routes_of_administration = ]


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
| bioavailability = | bioavailability =
| protein_bound = | protein_bound =
| metabolism = | metabolism =
| elimination_half-life = | elimination_half-life =
| excretion = | excretion =


<!--Identifiers--> <!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = | CAS_number = 180003-17-2
| ATC_prefix = none
| ATC_suffix = | ATC_prefix =
| ATC_suffix =
| PubChem = 6918373 | PubChem = 6918373
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = | DrugBank = DB04870
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 20153369 | ChemSpiderID = 5293576
| UNII = 64R56KMG1Z
| synonyms = Estrone 3-oleate; Estrone oleic acid; 17-Oxoestra-1,3,5(10)-trien-3-yl (9''Z'')-9-octadecenoate; Estra-1,3,5-trien-3-ol-17-one 3-((9''Z'')-octadec-9-enoate)


<!--Chemical data--> <!--Chemical data-->
| C=36 | H=54 | O=3 | C=36 | H=54 | O=3
⚫ | SMILES = CCCCCCCC\C=C/CCCCCCCC(=O)c3cc(O)cc4CC2(CC1(C)C(=O)CC12)c34
| molecular_weight = 534.812 g/mol
⚫ | smiles = CCCCCCCC\C=C/CCCCCCCC(=O)c3cc(O)cc4CC2(CC1(C)C(=O)CC12)c34
| InChI = 1/C36H54O3/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-33(38)31-26-28(37)25-27-19-20-29-30(35(27)31)23-24-36(2)32(29)21-22-34(36)39/h10-11,25-26,29-30,32,37H,3-9,12-24H2,1-2H3/b11-10-/t29-,30+,32+,36+/m1/s1
| InChIKey = JWLQYWPSIIMIFS-AAZNOHQBBY
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C36H54O3/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-33(38)31-26-28(37)25-27-19-20-29-30(35(27)31)23-24-36(2)32(29)21-22-34(36)39/h10-11,25-26,29-30,32,37H,3-9,12-24H2,1-2H3/b11-10-/t29-,30+,32+,36+/m1/s1 | StdInChI = 1S/C36H54O3/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-33(38)31-26-28(37)25-27-19-20-29-30(35(27)31)23-24-36(2)32(29)21-22-34(36)39/h10-11,25-26,29-30,32,37H,3-9,12-24H2,1-2H3/b11-10-/t29-,30+,32+,36+/m1/s1
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}} }}


'''Oleoyl-estrone''' (OE) is a ] ] of ]. It is a naturally circulating hormone in animals including humans. It was first reported in 1996 to cause a body fat loss effect in ]s in the ''International Journal of Obesity and Related Metabolic Disorders''.<ref>{{cite journal |author=Sanchis D, Balada F, del Mar Grasa M, ''et al.'' |title=Oleoyl-estrone induces the loss of body fat in rats |journal=Int. J. Obes. Relat. Metab. Disord. |volume=20 |issue=6 |pages=588–94 |year=1996 |month=June |pmid=8782737 }}</ref> The ] has all been conducted by the Nitrogen-Obesity Research Group of the ]. '''Oleoyl-estrone''' ('''OE'''), or '''estrone 3-oleate''', is a ] of ]. It is a naturally circulating hormone in animals, including humans. It was studied as a potential weight-loss drug, but failed to show benefit in clinical trials. It was first reported in 1996 to cause a body fat loss effect in ]s in the ''International Journal of Obesity and Related Metabolic Disorders''.<ref>{{cite journal |vauthors=Sanchis D, Balada F, del Mar Grasa M, etal |title=Oleoyl-estrone induces the loss of body fat in rats |journal=Int. J. Obes. Relat. Metab. Disord. |volume=20 |issue=6 |pages=588–94 |date=June 1996 |pmid=8782737 }}</ref> The ] has all been conducted by the Nitrogen-Obesity Research Group of the ].


The compound was found to potently induce body-fat loss while preserving ] stores in animals which is the ultimate goal of an ] as body protein loss is an undesired but inevitable (to some degree) side effect of fat loss via ] restriction. The compound was found to potently induce body-fat loss while preserving ] stores in animals which is the ultimate goal of an ] as body protein loss is an undesired but inevitable (to some degree) side effect of fat loss via ] restriction.


==Operation == ==Mechanism of action ==
Oleoyl-estrone functions by reducing energy-intake without prescribed dietary restriction (forced dietary restriction in addition to OE actually led to protein losses) while maintaining energy expenditure (which normally falls as part of the adaptations to calorie restriction). The partitioning effects of this ] leads to ] stores being the source of energy that makes up for the energy deficit rather than protein stores. Oleoyl-estrone functions by reducing energy-intake without prescribed dietary restriction (forced dietary restriction in addition to OE actually led to protein losses) while maintaining energy expenditure (which normally falls as part of the adaptations to calorie restriction). The partitioning effects of this ] leads to ] stores being the source of energy that makes up for the energy deficit rather than protein stores.


==Research== ==Research==
The ] has been widely studied in various strains of animals and shown to be effective in virtually all studies. A surprising result that came out of the animal studies was that OE treated animals maintained their fat loss after treatment was stopped. Weight loss maintenance is one of the most difficult aspects of obesity treatment and so this effect is promising. This led to the postulation that oleoyl-estrone can reduce the body's bodyfat setpoint which would allow the body to maintain a reduced bodyfat without experiencing a hormonal milieu that aims to regain the lost bodyfat by reducing energy expenditure and increasing energy intake. The molecule has been widely studied in various strains of animals and shown to be effective in virtually all studies. A surprising result that came out of the animal studies was that OE treated animals maintained their fat loss after treatment was stopped. Weight loss maintenance is one of the most difficult aspects of obesity treatment and so this effect is promising. This led to the postulation that oleoyl-estrone can reduce the body's bodyfat setpoint which would allow the body to maintain a reduced bodyfat without experiencing a hormonal milieu that aims to regain the lost bodyfat by reducing energy expenditure and increasing energy intake.


The research group discovered that oleoyl-estrone levels correlated with bodyfat stores except for ] ]s where there was less oleoyl-estrone circulating than would be predicted based on bodyfat levels. This led to the theory that administering oleoyl-estrone to bring ] OE levels up to normal would signal to the body that there is an excess amount of bodyfat and therefore there would be a bodyfat loss. The research group discovered that oleoyl-estrone levels correlated with bodyfat stores except for ] ]s where there was less oleoyl-estrone circulating than would be predicted based on bodyfat levels. This led to the theory that administering oleoyl-estrone to bring ] OE levels up to normal would signal to the body that there is an excess amount of bodyfat and therefore there would be a bodyfat loss.


Recent research shows that corticosterone inhibits the fat mobilizing effects of oleoyl-estrone in female rats that had their adrenal glands removed. <ref>{{cite journal |author=del Mar Grasa M, Serrano M, Fernández-López JA, Alemany M |title=Corticosterone inhibits the lipid-mobilizing effects of oleoyl-estrone in adrenalectomized rats |journal=Endocrinology |volume=148 |issue=8 |pages=4056–63 |year=2007 |month=August |pmid=17510239 |doi=10.1210/en.2007-0331 |url=http://endo.endojournals.org/cgi/pmidlookup?view=long&pmid=17510239}}</ref> Recent research shows that corticosterone inhibits the fat mobilizing effects of oleoyl-estrone in female rats that had their adrenal glands removed.<ref>{{cite journal |vauthors=del Mar Grasa M, Serrano M, Fernández-López JA, Alemany M |title=Corticosterone inhibits the lipid-mobilizing effects of oleoyl-estrone in adrenalectomized rats |journal=Endocrinology |volume=148 |issue=8 |pages=4056–63 |date=August 2007 |pmid=17510239 |doi=10.1210/en.2007-0331 |hdl=2445/22225 |url=http://endo.endojournals.org/cgi/pmidlookup?view=long&pmid=17510239|doi-access=free |hdl-access=free }}</ref>


The research group set up a company called in 2001 which included as a founder Dr. Marià Alemany, one of the principal researches, who is also the holder of a 1998 U.S. patent ({{US patent|5798348}}) for fatty acid esters of estrone, including OE, in relation to fat loss. The research group set up a company called Oleoyl-Estrone Developments in 2001 which included as a founder Marià Alemany, one of the principal researches, who is also the holder of a 1998 U.S. patent ({{US patent|5798348}}) for fatty acid esters of estrone, including OE, in relation to fat loss.


The group studied the effects of ] OE on Dr. Marià Alemany who was ]. It was shown for the first time to be effective at producing fat loss in a human and also a maintenance (and increase) of weight loss in two-month rest periods in between three-week dosing periods. This was achieved with no prescribed dietary restrictions.<ref>{{cite paper The group studied the effects of ] OE on Marià Alemany who was ]. It was shown for the first time to be effective at producing fat loss in a human and also a maintenance (and increase) of weight loss in two-month rest periods in between three-week dosing periods. This was achieved with no prescribed dietary restrictions.<ref>{{cite web
| author =Marià Alemany PhD et al. | author =Marià Alemany| title =Oleoyl-estrone-induced weight loss in an obese man
| title =Oleoyl-estrone-induced weight loss in an obese man
| publisher =Manhattan Pharmaceuticals Inc. | publisher =Manhattan Pharmaceuticals Inc.
| url =http://www.manhattanpharma.com/oe-ma6.pdf | url =http://www.manhattanpharma.com/oe-ma6.pdf
⚫ | access-date = 2007-04-04 |archive-url = https://web.archive.org/web/20070316040624/http://www.manhattanpharma.com/oe-ma6.pdf <!-- Bot retrieved archive --> |archive-date = 2007-03-16|display-authors=etal}}</ref>
| format =pdf
⚫ | accessdate = 2007-04-04 |archiveurl = http://web.archive.org/web/20070316040624/http://www.manhattanpharma.com/oe-ma6.pdf <!-- Bot retrieved archive --> |archivedate = 2007-03-16}}</ref>


==Clinical development== ==Clinical development==
OE was licensed in an exclusive worldwide deal to in 2002. An Investigational New Drug application was accepted by the ] (FDA) in 2005 and a Phase I trial was conducted in Switzerland. The results showed OE to be safe and to lead to weight loss after just 7 days of dosing, and this weight loss was maintained for three further weeks after treatment had stopped. OE was licensed to Manhattan Pharmaceuticals in 2002. An ] application was accepted by the ] (FDA) in 2005 and a Phase I trial was conducted in Switzerland. The results showed OE to be safe and to lead to weight loss after just 7 days of dosing, and this weight loss was maintained for three further weeks after treatment had stopped.


In June 2006 a Phase IIa trial of 100 ]s began which included two 14-day dosing periods each followed by 28 days of no treatment which was designed to elucidate the best dosing methods and in particular the maintenance of weight loss that had been shown. This trial was originally a single-centre trial in Switzerland, but in November 2006 it was announced that the trial had been expanded to two additional clinical sites in the USA.<ref>{{cite press release In June 2006, a Phase IIa trial of 100 ]s began which included two 14-day dosing periods each followed by 28 days of no treatment which was designed to elucidate the best dosing methods and in particular the maintenance of weight loss that had been shown. This trial was originally a single-centre trial in Switzerland, but in November 2006 it was announced that the trial had been expanded to two additional clinical sites in the USA.<ref>{{cite press release
| title =Manhattan Pharmaceuticals Expands Phase 2a Obesity Clinical Trial Sites to US | title =Manhattan Pharmaceuticals Expands Phase 2a Obesity Clinical Trial Sites to US
| publisher =Manhattan Pharmaceuticals, Inc. | publisher =Manhattan Pharmaceuticals, Inc.
| date =November 8, 2006 | date =November 8, 2006
| url =http://www.manhattanpharma.com/pr_110806.html | url =http://www.manhattanpharma.com/pr_110806.html
⚫ | access-date = 2007-04-04}}</ref> An additional trial was commenced in October 2006 that is designed to investigate the efficacy of the drug in morbidly obese patients who had been designated as ] patient candidates.<ref>{{cite press release
| accessdate = 2007-04-04}}</ref> The results from this trial are expected in the first half of 2007.

⚫ An additional trial was commenced in October 2006 that is designed to investigate the efficacy of the drug in morbidly obese patients who had been designated as ] patient candidates.<ref>{{cite press release
| title =Manhattan Pharmaceuticals Expanding Oral Oleoyl-Estrone Clinical Program To Include Morbidly Obese | title =Manhattan Pharmaceuticals Expanding Oral Oleoyl-Estrone Clinical Program To Include Morbidly Obese
| publisher =Manhattan Pharmaceuticals, Inc. | publisher =Manhattan Pharmaceuticals, Inc.
| date =October 12, 2006 | date =October 12, 2006
| url =http://www.manhattanpharma.com/pr_101206.html | url =http://www.manhattanpharma.com/pr_101206.html
| accessdate = 2007-04-04}}</ref> | access-date = 2007-04-04}}</ref>
This trial, taking place in the USA, will recruit 24 patients and will dose OE for 30 days, without any break, and then have a follow-up 30 days after dosing has been completed. The results from this trial are also expected in the first half of 2007. This trial which took place in the United States, recruited 24 patients and dosed OE for 30 days, without any break, followed by 30 days of evaluation after dosing completed.


On July 10, 2007 Manhattan Pharmaceuticals announced that its phase 2a studies for oral oleoyl-estrone failed. The two studies demonstrated no clinically meaningful or statistically significant placebo adjusted weight loss.<ref>http://www.emaxhealth.com/95/13821.html</ref> On July 10, 2007, Manhattan Pharmaceuticals announced that its phase 2a studies for oral oleoyl-estrone failed. The two studies demonstrated no clinically meaningful or statistically significant placebo adjusted weight loss.<ref>{{Cite web | url=http://www.emaxhealth.com/95/13821.html | archive-url=https://web.archive.org/web/20131104100916/http://www.emaxhealth.com/95/13821.html | archive-date=2013-11-04 | title=Phase 2a Studies For Oral Oleoyl-Estrone Failed}}</ref>

==See also==
* ]


==References== ==References==
{{reflist}} {{Reflist|2}}

==External links==
* Drug development company that was formerly developing OE
* Research company that licensed OE to Manhattan Pharmaceuticals


{{Antiobesity preparations}} {{Antiobesity preparations}}
{{Estrogen receptor modulators}}


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