Erteberel

Erteberel (INN, USAN; 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 is under development by Eli Lilly for the treatment of schizophrenia.[2][3][4] It is specifically under investigation for the treatment of negative symptoms and cognitive impairment associated with the condition.[2] As of 2015, it is in phase II clinical trials for this indication in the United States.[2] 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.[2][5] The drug has also been proposed as a potential novel treatment for glioblastoma.[6]

Erteberel
Clinical data
Other namesSelective 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[1]
Routes of
administration		By mouth
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18H18O3
Molar mass282.339 g·mol−1
3D model (JSmol)

Erteberel has 14-fold binding selectivity for the ERβ over the ERα (Ki = 0.19 nM versus 2.68 nM, respectively).[3][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).[7] It is roughly a full agonist of both the ERβ and ERα (Emax = 101% versus 94%, respectively).[3][7] 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

References
  1. Paterni I, Bertini S, Granchi C, Macchia M, Minutolo F (2013). "Estrogen receptor ligands: a patent review update". Expert Opin Ther Pat. 23 (10): 1247–71. doi:10.1517/13543776.2013.805206. PMID 23713677. S2CID 6259593.
  2. https://adisinsight.springer.com/drugs/800031986%5B%5D
  3. Minutolo F, Macchia M, Katzenellenbogen BS, Katzenellenbogen JA (2011). "Estrogen receptor β ligands: recent advances and biomedical applications". Med Res Rev. 31 (3): 364–442. doi:10.1002/med.20186. PMID 19967775. S2CID 3841877.
  4. Nilsson S, Koehler KF, Gustafsson JÅ (2011). "Development of subtype-selective oestrogen receptor-based therapeutics". Nat Rev Drug Discov. 10 (10): 778–92. doi:10.1038/nrd3551. PMID 21921919. S2CID 23043739.
  5. Roehrborn CG, Spann ME, Myers SL, Serviss CR, Hu L, Jin Y (2015). "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. doi:10.1038/pcan.2014.43. PMID 25348255. S2CID 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 (2016). "Selective Estrogen Receptor β Agonist LY500307 as a Novel Therapeutic Agent for Glioblastoma". Sci Rep. 6: 24185. doi:10.1038/srep24185. PMC 4850367. PMID 27126081.
  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 (2006). "Benzopyrans are selective estrogen receptor beta agonists with novel activity in models of benign prostatic hyperplasia". J. Med. Chem. 49 (21): 6155–7. doi:10.1021/jm060491j. PMID 17034120.
  8. Hu L, Jin Y, Li YG, Borel A (2015). "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. doi:10.1002/cpdd.184. PMID 27136911. S2CID 21086262.



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