Erteberel (
INNTooltip International Nonproprietary Name,
USANTooltip 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,
nonsteroidalestrogen which acts as a selective
ERβagonist 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 IIclinical 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 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
gonadaltestosterone production in men.[8]
^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.
PMID25348255.
S2CID9315809.
^
abcNorman 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.
PMID17034120.