Erteberel (, ; former developmental code name LY-500307; also known as selective estrogen receptor beta agonist-1 or SERBA-1) is a
synthetic,
nonsteroidal A nonsteroidal compound is a drug that is not a steroid nor a steroid derivative. Nonsteroidal anti-inflammatory drugs (NSAIDs) are distinguished from corticosteroids as a class of anti-inflammatory agents.
List of nonsteroidal steroid receptor mo ...
estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal a ...
which acts as a selective
ERβ
Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by ...
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
and is under development by
Eli Lilly
Eli Lilly (July 8, 1838 – June 6, 1898) was an American soldier, pharmacist, chemist, and businessman who founded the Eli Lilly and Company pharmaceutical corporation. Lilly enlisted in the Union Army during the American Civil War and r ...
for the treatment of
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wi ...
.
It is specifically under investigation for the treatment of
negative symptoms
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
and
cognitive impairment
Cognitive deficit is an inclusive term to describe any characteristic that acts as a barrier to the cognition process.
The term may describe
* deficits in overall intelligence (as with intellectual disabilities),
* specific and restricted defic ...
associated with the condition.
As of 2015, it is in
phase II clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s for this indication in the
United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., federal district, five ma ...
.
Erteberel was also under investigation for the treatment of
benign prostatic hyperplasia
Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss ...
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.
The drug has also been proposed as a potential novel treatment for
glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality cha ...
.
Erteberel has 14-fold
binding selectivity
Binding selectivity is defined with respect to the binding of ligands to a substrate forming a complex. Binding selectivity describes how a ligand may bind more preferentially to one receptor than another. A selectivity coefficient is the equil ...
for the ERβ over the
ERα
Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein)
that is activated by the sex h ...
(K
i = 0.19 nM versus 2.68 nM, respectively).
However, it shows 32-fold
functional selectivity
Functional selectivity (or “agonist trafficking”, “biased agonism”, “biased signaling”, "ligand bias" and “differential engagement”) is the ligand-dependent selectivity for certain signal transduction pathways relative to a referen ...
for activation of the ERβ over the ERα (
EC50 = 0.66 nM versus 19.4 nM, respectively).
It is roughly a
full agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...
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
gonad
A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces ...
al
testosterone
Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteris ...
production in men.
See also
*
List of investigational sex-hormonal agents § Estrogenics
*
List of investigational antipsychotics
This is a list of investigational antipsychotics, or antipsychotics that are currently under development for clinical use but are not yet approved. ''Chemical/generic names are listed first, with developmental code names, synonyms, and brand names ...
*
Estrogen receptor beta § Agonists
References
External links
Erteberel - AdisInsight
Antipsychotics
Benzopyrans
Cyclopentanes
Diols
Selective ERβ agonists
Synthetic estrogens
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