Erteberel
{{Short description|Chemical compound}}
{{Drugbox
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| IUPAC_name = (3aS,4R,9bR)-4-(4-Hydroxyphenyl)-1,2,3,3a,4,9b-hexahydrocyclopenta[c]chromen-8-ol
| image = Erteberel skeletal.svg
| width = 250px
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| routes_of_administration = By mouth
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| 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; (2R,3S,4R)-SERBA{{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 }}
| 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, nonsteroidal estrogen which acts as a selective ERβ agonist and was under development by Eli Lilly for the treatment of schizophrenia.{{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}}{{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 }}{{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 }} It was specifically under investigation for the treatment of negative symptoms and cognitive impairment associated with the condition. It managed to reach phase II clinical trials for this indication in the United States in 2015. As of 2021 development has been discontinued.{{cite web | url=https://adisinsight.springer.com/drugs/800031986 | title=Erteberel - Eli Lilly and Company - AdisInsight }} 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.{{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 }} The drug has also been proposed as a potential novel treatment for glioblastoma.{{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 }}
Erteberel has 14-fold binding selectivity for the ERβ over the ERα (Ki = 0.19 nM versus 2.68 nM, respectively).{{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 }} However, it shows 32-fold functional selectivity for activation of the ERβ over the ERα (EC50 = 0.66 nM versus 19.4 nM, respectively). It is roughly a full agonist of both the ERβ and ERα (Emax = 101% versus 94%, respectively). Although selective for the ERβ, erteberel loses its selectivity at high dosages and activates the ERα as well, producing effects such as suppression of gonadal testosterone production in men.{{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 }}
See also
References
{{Reflist|2}}
External links
- [https://web.archive.org/web/20161231170122/https://adisinsight.springer.com/drugs/800031986 Erteberel - AdisInsight]
{{Estrogen receptor modulators}}
Category:Selective ERβ agonists
Category:Experimental antidepressants
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