Erteberelのソースを表示

{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = 
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| IUPAC_name = (3a''S'',4''R'',9b''R'')-4-(4-Hydroxyphenyl)-1,2,3,3a,4,9b-hexahydrocyclopenta[''c'']chromen-8-ol
| image = Erteberel skeletal.svg
| width = 250px

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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
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| routes_of_administration = [[Oral administration|By mouth]]

<!--Pharmacokinetic data-->
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<!-- Identifiers -->
| CAS_number_Ref = 
| CAS_number = 533884-09-2
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| PubChem = 10286159
| IUPHAR_ligand = 
| DrugBank_Ref = 
| DrugBank = DB07933
| ChemSpiderID_Ref = 
| ChemSpiderID = 8461628
| UNII = 2ZUL6758TZ
| KEGG = D09899
| ChEBI = 231600
| ChEMBL = 278703
| synonyms = Selective estrogen receptor beta agonist-1; SERBA-1; LY-500307; (3aS,4R,9bR)-1,2,3,3a,4,9b-Hexahydro-4-(4-hydroxyphenyl)cyclopenta(c)(1)benzopyran-8-ol; (2''R'',3''S'',4''R'')-SERBA<ref name="pmid23713677">{{cite journal | vauthors = Paterni I, Bertini S, Granchi C, Macchia M, Minutolo F | title = Estrogen receptor ligands: a patent review update | journal = Expert Opin Ther Pat | volume = 23 | issue = 10 | pages = 1247–71 | year = 2013 | pmid = 23713677 | doi = 10.1517/13543776.2013.805206 | s2cid = 6259593 }}</ref>

<!--Chemical data-->
| C=18 | H=18 | O=3
| SMILES = C1C[C@H]2[C@@H](C1)C3=C(C=CC(=C3)O)O[C@H]2C4=CC=C(C=C4)O
| StdInChI_Ref = 
| StdInChI = 1S/C18H18O3/c19-12-6-4-11(5-7-12)18-15-3-1-2-14(15)16-10-13(20)8-9-17(16)21-18/h4-10,14-15,18-20H,1-3H2/t14-,15+,18+/m1/s1
| StdInChIKey_Ref = 
| StdInChIKey = XIESSJVMWNJCGZ-VKJFTORMSA-N
}}

'''Erteberel''' ({{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}; former developmental code name '''LY-500307'''; also known as '''selective estrogen receptor beta agonist-1''' or '''SERBA-1''') is a [[synthetic compound|synthetic]], [[nonsteroidal]] [[estrogen]] which acts as a selective [[ERβ]] [[agonist]] and was under development by [[Eli Lilly and Company|Eli Lilly]] for the treatment of [[schizophrenia]].<ref name="AdisInsight">{{cite web |url=https://adisinsight.springer.com/drugs/800031986 |title=Erteberel - AdisInsight |website=adisinsight.springer.com |access-date=22 May 2022 |archive-url=https://web.archive.org/web/20161231170122/https://adisinsight.springer.com/drugs/800031986 |archive-date=31 December 2016 |url-status=dead}}</ref><ref name="pmid19967775">{{cite journal | vauthors = Minutolo F, Macchia M, Katzenellenbogen BS, Katzenellenbogen JA | title = Estrogen receptor β ligands: recent advances and biomedical applications | journal = Med Res Rev | volume = 31 | issue = 3 | pages = 364–442 | year = 2011 | pmid = 19967775 | doi = 10.1002/med.20186 | s2cid = 3841877 }}</ref><ref name="pmid21921919">{{cite journal | vauthors = Nilsson S, Koehler KF, Gustafsson JÅ | title = Development of subtype-selective oestrogen receptor-based therapeutics | journal = Nat Rev Drug Discov | volume = 10 | issue = 10 | pages = 778–92 | year = 2011 | pmid = 21921919 | doi = 10.1038/nrd3551 | s2cid = 23043739 }}</ref> It was specifically under investigation for the treatment of [[negative symptoms]] and [[cognitive impairment]] associated with the condition.<ref name="AdisInsight" /> It managed to reach [[Phases of clinical research#Phase II|phase II]] [[clinical trial]]s for this indication in the [[United States]] in 2015.<ref name="AdisInsight" /> As of 2021 development has been discontinued.<ref>{{cite web | url=https://adisinsight.springer.com/drugs/800031986 | title=Erteberel - Eli Lilly and Company - AdisInsight }}</ref> Erteberel was also under investigation for the treatment of [[benign prostatic hyperplasia]] and reached phase II clinical studies for this use but failed to improve symptoms in men with the condition and development for this indication was discontinued.<ref name="AdisInsight" /><ref name="pmid25348255">{{cite journal | vauthors = Roehrborn CG, Spann ME, Myers SL, Serviss CR, Hu L, Jin Y | title = Estrogen receptor beta agonist LY500307 fails to improve symptoms in men with enlarged prostate secondary to benign prostatic hypertrophy | journal = Prostate Cancer Prostatic Dis. | volume = 18 | issue = 1 | pages = 43–8 | year = 2015 | pmid = 25348255 | doi = 10.1038/pcan.2014.43 | s2cid = 9315809 }}</ref> The drug has also been proposed as a potential novel treatment for [[glioblastoma]].<ref name="pmid27126081">{{cite journal | vauthors = Sareddy GR, Li X, Liu J, Viswanadhapalli S, Garcia L, Gruslova A, Cavazos D, Garcia M, Strom AM, Gustafsson JA, Tekmal RR, Brenner A, Vadlamudi RK | title = Selective Estrogen Receptor β Agonist LY500307 as a Novel Therapeutic Agent for Glioblastoma | journal = Sci Rep | volume = 6 | pages = 24185 | year = 2016 | pmid = 27126081 | pmc = 4850367 | doi = 10.1038/srep24185 | bibcode = 2016NatSR...624185S }}</ref>

Erteberel has 14-fold [[binding selectivity]] for the ERβ over the [[ERα]] (K<sub>i</sub> = 0.19&nbsp;nM versus 2.68&nbsp;nM, respectively).<ref name="pmid19967775" /><ref name="pmid17034120">{{cite journal | vauthors = Norman BH, Dodge JA, Richardson TI, Borromeo PS, Lugar CW, Jones SA, Chen K, Wang Y, Durst GL, Barr RJ, Montrose-Rafizadeh C, Osborne HE, Amos RM, Guo S, Boodhoo A, Krishnan V | title = Benzopyrans are selective estrogen receptor beta agonists with novel activity in models of benign prostatic hyperplasia | journal = J. Med. Chem. | volume = 49 | issue = 21 | pages = 6155–7 | year = 2006 | pmid = 17034120 | doi = 10.1021/jm060491j }}</ref> However, it shows 32-fold [[functional selectivity]] for activation of the ERβ over the ERα ([[EC50|EC<sub>50</sub>]] = 0.66&nbsp;nM versus 19.4&nbsp;nM, respectively).<ref name="pmid17034120" /> It is roughly a [[full agonist]] of both the ERβ and ERα ([[intrinsic activity|E<sub>max</sub>]] = 101% versus 94%, respectively).<ref name="pmid19967775" /><ref name="pmid17034120" /> Although selective for the ERβ, erteberel loses its selectivity at high dosages and activates the ERα as well, producing effects such as suppression of [[gonad]]al [[testosterone]] production in men.<ref name="pmid27136911">{{cite journal | vauthors = Hu L, Jin Y, Li YG, Borel A | title = Population pharmacokinetic/pharmacodynamic assessment of pharmacological effect of a selective estrogen receptor β agonist on total testosterone in healthy men | journal = Clinical Pharmacology in Drug Development | volume = 4 | issue = 4 | pages = 305–14 | year = 2015 | pmid = 27136911 | doi = 10.1002/cpdd.184 | s2cid = 21086262 | doi-access = free }}</ref>

==See also==
* [[List of investigational sex-hormonal agents#Estrogenics|List of investigational sex-hormonal agents § Estrogenics]]
* [[List of investigational antipsychotics]]
* [[Estrogen receptor beta#Agonists|Estrogen receptor beta § Agonists]]

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

==External links==
* [https://web.archive.org/web/20161231170122/https://adisinsight.springer.com/drugs/800031986 Erteberel - AdisInsight]

{{Estrogen receptor modulators}}

[[Category:Antipsychotics]]
[[Category:Benzopyrans]]
[[Category:Cyclopentanes]]
[[Category:Diols]]
[[Category:Selective ERβ agonists]]
[[Category:Synthetic estrogens]]
[[Category:Experimental antidepressants]]


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