Molecule

Description

Cancer

Description

Andarine (GTX-007) is a selective nonsteroidal androgen receptor (AR) agonist with K_i of 4 nM.

Targets

IC₅₀

In Vitro

Andarine stimulates AR-mediated transcription to 93% of that observed for 1 nM DHT at a concentration of 10 nM. ^[1]

In Vivo

Andarine exhibits potent and efficacious anabolic activity and results in dose-dependent stimulation of growth in prostate, seminal vesicles, and levator ani muscle with the ED50 of 0.43 mg/day, 0.55 mg/day, and 0.14 mg/day, respectively. Besides, Andarine shows no dose-dependent effect on castration-induced change in FSH, and partially suppresses LH production at dose rates of 0.5 mg/day or higher. ^[1] In dogs administrated by intravenous doses of Andarine (0.1, 1, 3, and 10 mg/kg), the total body clearance (CL) ranged from 7.4 mL/min/kg to 3.1 mL/min/kg, volume of distribution at steady state (Vss) is 1.39 L/kg and half-life of Andarine is 229 minutes, respectively. In addition, oral bioavailability is 38%, 62% and 91% for the 10 mg/kg, 1 mg/kg and 0.1 mg/kg doses, respectively. ^[2] Andarine demonstrates tissue-selective pharmacological activity and significantly decreased prostate weight to 79.4% at a concentration of 0.5 mg/day in intact rats. ^[3]

Clinical Trials

Features

In Vitro Pharmacological Activity

Cytosolic AR is prepared from ventral prostates of castrated male Sprague-Dawley rats (about 250 g). The binding affinity of compounds 1, 2, 3, and 4 to the AR preparation is determined and analyzed as Mukherjee et al.in 1996. AR binding affinities of the synthesized ligands are determined by competitive binding in the presence of the high-affinity AR ligand [³H]MIB. AR binding studies are performed by incubating increasing concentrations (10_?3 nM to 10,000 nM) of each ligand with cytosol and a saturating concentration of [³H]MIB (1 nM) at 4 °C for 18 hours. In preliminary experiments, the equilibrium dissociation constant (K_d) of MIB is determined under identical conditions by incubating increasing concentrations of [₃H]MIB (0.01 nM to 10 nM) with cytosol. The minimum concentration of [₃H]MIB required to saturate AR sites in the cytosol preparation is 1 nM. Subsequent experiments use either 1 nM or 2 nM [₃H]MIB. The incubation mixtures also contains 1000 nM triamcinolone acetonide to block the interaction of MIB with progesterone receptors. For the determination of nonspecific binding, separate experiments are conducted by adding 1000 nM MIB to the incubation mixture. Separation of bound and free radioactivity at the end of incubation is achieved by the HAP method, and 0.8 mL of the ethanolic supernatant is added to 5 mL of scintillation fluid. Radioactivity is counted in a Beckman LS 6800 liquid scintillation counter. The ability of the compounds to influence AR-mediated transcriptional activation is examined using a cotransfection system. Transcriptional activation is measured using a single concentration (10 nM) of the indicated compound and reported as a percentage of the transcriptional activation observed for 1 nM DHT.

Animal Models

Male Sprague-Dawley rats and castrated rat model.

Formulation

Andarine is dissolved in minimal amounts of ethanol and then diluted to final concentrations with PEG 300.

Doses

≤1 mg/day

Administration

Administered via osmotic pump.