Galeterone (developmental code names TOK-001, VN/124-1) is a
steroidal antiandrogen
A steroidal antiandrogen (SAA) is an antiandrogen with a steroidal chemical structure. They are typically receptor antagonist, antagonists of the androgen receptor (AR) and act both by receptor antagonist, blocking the effects of androgens like ...
which was under development by Tokai Pharmaceuticals for the treatment of
prostate cancer
Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...
. It possesses a unique triple
mechanism of action
In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...
, acting as an
androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...
antagonist
An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.CYP17A1 inhibitor, the latter of which prevents the
biosynthesis
Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...
of
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
s. As a CYP17A1 inhibitor, galeterone shows selectivity for 17,20-lyase over 17α-hydroxylase.
Prostate cancer drug abiraterone and its analog galeterone are Δ5,3β-hydroxy steroids. Structures of these two agents are identical to endogenous steroid substrates (cholesterole, dehydroepiandorosterone and pregnenolone) for the 3β-hydroxysteroid dehydrogenase (3βHSD) of endocrine system. It has been reported that both of these agents are metabolized to 3-oxo-Δ4-steroids by 3βHSD in short period on oral administration. First metabolite 3-oxo-Δ4-abiraterone has more potent anti-prostate cancer properties than abiraterone where galeterone metabolite (3-oxo-Δ4-galaterone) has activity comparable to parent. Further these two metabolites undergo metabolism by 5α-reductase (5α-SRD) of endocrine system which leads to five more biologically inactive metabolites. It is known that galeterone has poor oral bioavailability in rodents. Poor pharmacokinetic properties (oral absorption and metabolic half-life) of galeterone may be the reason for its clinical compromise.
Galeterone, along with
abiraterone acetate
Abiraterone acetate, sold under the brand name Zytiga among others, is a medication used to treat prostate cancer. Specifically it is used together with a corticosteroid for metastatic castration-resistant prostate cancer (mCRPC) and metasta ...
steroid
A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration.
Steroids have two principal biological functions: as important components of cell membranes t ...
s and compounds, with Ki values in the sub-micromolar range.
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 ...
(ARMOR3-SV) for AR-V7-expressing metastatic castration-resistant prostate cancer. Tokai announced the discontinuation of ARMOR3-SV on July 26, 2016, after a data monitoring committee determined that the trial was unlikely to meet its endpoint. On August 22, 2016, the company announced the discontinuation of their phase II expansion (ARMOR2) as well.
In August 2017, Tokai Pharmaceuticals discontinued the development of galeterone. On December 17, 2018, it was announced that Educational & Scientific, LLC (ESL), in conjunction with
University of Maryland
The University of Maryland, College Park (University of Maryland, UMD, or simply Maryland) is a public land-grant research university in College Park, Maryland, United States. Founded in 1856, UMD is the flagship institution of the Univ ...