Erteberel Explained

Erteberel (; 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.^{[1] [2] [3]} 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.^[4] 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.^[5] The drug has also been proposed as a potential novel treatment for glioblastoma.^[6]

Erteberel has 14-fold binding selectivity for the ERβ over the ERα (K_i = 0.19 nM versus 2.68 nM, respectively).^[7] 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 (E_max = 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.^[8]

See also

• List of investigational sex-hormonal agents § Estrogenics
• List of investigational antipsychotics
• Estrogen receptor beta § Agonists

External links

• Erteberel - AdisInsight

Notes and References

1. Web site: Erteberel - AdisInsight . adisinsight.springer.com . 22 May 2022 . https://web.archive.org/web/20161231170122/https://adisinsight.springer.com/drugs/800031986 . 31 December 2016 . dead.
2. Minutolo F, Macchia M, Katzenellenbogen BS, Katzenellenbogen JA . Estrogen receptor β ligands: recent advances and biomedical applications . Med Res Rev . 31 . 3 . 364–442 . 2011 . 19967775 . 10.1002/med.20186 . 3841877 .
3. Nilsson S, Koehler KF, Gustafsson JÅ . Development of subtype-selective oestrogen receptor-based therapeutics . Nat Rev Drug Discov . 10 . 10 . 778–92 . 2011 . 21921919 . 10.1038/nrd3551 . 23043739 .
4. Web site: Erteberel - Eli Lilly and Company - AdisInsight .
5. Roehrborn CG, Spann ME, Myers SL, Serviss CR, Hu L, Jin Y . Estrogen receptor beta agonist LY500307 fails to improve symptoms in men with enlarged prostate secondary to benign prostatic hypertrophy . Prostate Cancer Prostatic Dis. . 18 . 1 . 43–8 . 2015 . 25348255 . 10.1038/pcan.2014.43 . 9315809 .
6. 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 . Selective Estrogen Receptor β Agonist LY500307 as a Novel Therapeutic Agent for Glioblastoma . Sci Rep . 6 . 24185 . 2016 . 27126081 . 4850367 . 10.1038/srep24185 . 2016NatSR...624185S .
7. 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 . Benzopyrans are selective estrogen receptor beta agonists with novel activity in models of benign prostatic hyperplasia . J. Med. Chem. . 49 . 21 . 6155–7 . 2006 . 17034120 . 10.1021/jm060491j .
8. Hu L, Jin Y, Li YG, Borel A . Population pharmacokinetic/pharmacodynamic assessment of pharmacological effect of a selective estrogen receptor β agonist on total testosterone in healthy men . Clinical Pharmacology in Drug Development . 4 . 4 . 305–14 . 2015 . 27136911 . 10.1002/cpdd.184 . 21086262 . free .