Ostarine (MK-2866)

Ostarine (MK-2866), also called enobosarm or GTx-024, is a nonsteroidal selective androgen receptor modulator, or SARM. GTx, Inc. took it into phase 3 trials for cancer-related muscle wasting and phase 2 trials for breast cancer and stress urinary incontinence (Narayanan et al., 2018).

PubChem CID 11326715 (titled Enobosarm) gives the same formula and weight and is the source of the CAS number, structure and aliases.

Ostarine research falls into five areas, each summarized with its model. Human data come from clinical trials, most sponsored by GTx, and case reports; the rest is animal and cell work.

Tissue selectivity in animal models

Tissue selectivity was first shown in the Hershberger assay: in castrated rats, aryl-propionamide SARMs restored levator ani muscle weight to sham levels but only partly restored prostate and seminal vesicle weight, and enobosarm became the series' most advanced clinical candidate. The levator ani endpoint is criticized because that muscle is unusually rich in androgen receptors (Narayanan et al., 2018).

Selectivity has limits. In ovariectomized mice, seven days of GTx-024 raised uterine weight and uterine cell proliferation, mirroring dihydrotestosterone, while andarine had minimal effect (Simitsidellis et al., 2019). Ovariectomized rats showed heavier uteri at 0.4 and 4 mg/kg a day (Roch et al., 2020). Models: castrated rats, ovariectomized mice and rats (animal data only).

Rat and cell studies

In rats, radiolabeled GTx-024 was completely absorbed by mouth and cleared mainly in feces, with a plasma radioactivity half-life of 0.6 hours in males and 16.4 hours in females (Kim et al., 2013). In ovariectomized rats, five weeks at 0.4 or 4 mg/kg a day raised bone mineral density without significant biomechanical change (Hoffmann et al., 2019), and left muscle fiber size unchanged while capillary density rose (Roch et al., 2020).

In C2C12 and L6 muscle cells, ostarine raised proliferation and differentiation markers (myogenin, MyoD) through the androgen receptor and ERK1/2; male rats given 0.4 mg/kg daily for 30 days showed the same marker rise and higher muscle mass (Leciejewska et al., 2022). Models: rats and cell lines (animal and cell data only).

Muscle wasting trials

In a 12-week phase 2 trial, 120 healthy men over 60 and postmenopausal women received placebo or one of four daily amounts of GTx-024. Lean body mass, the primary endpoint, rose in step with the amount given, and a physical function measure rose at the highest amount; all authors worked for GTx (Dalton et al., 2011). In 159 people with cancer-related muscle wasting given placebo or one of two daily amounts for up to 113 days, lean body mass rose from baseline in both enobosarm arms but not with placebo (Dobs et al., 2013).

The phase 3 POWER 1 and 2 trials enrolled people starting chemotherapy for non-small-cell lung cancer, with day-84 stair climb power and lean body mass as co-primary endpoints (Crawford et al., 2016). Reviews report that muscle mass rose in both trials while physical function rose only marginally or not significantly (Narayanan et al., 2018; Christiansen et al., 2020). Models: randomized human trials.

Breast cancer and stress urinary incontinence

In a phase 2 trial published in 2024, 136 postmenopausal women with androgen receptor-positive, estrogen receptor-positive, HER2-negative advanced breast cancer were randomized to one of two daily amounts; at 24 weeks, 32 and 29 percent of evaluable women had a response or stable disease, the primary endpoint (Palmieri et al., 2024). A phase 2 trial pairing enobosarm with pembrolizumab in AR-positive triple-negative breast cancer stopped early when the GTx-024 supply was withdrawn (Yuan et al., 2021).

GTx-024 restored pelvic floor muscle weight in ovariectomized mice (Ponnusamy et al., 2017), but the phase 2 ASTRID trial in postmenopausal women with stress urinary incontinence missed its primary endpoint, and two further phase 2 studies were terminated the same month (Christiansen et al., 2020). Models: human trials and ovariectomized mice.

Adverse findings

In the 12-week trial in older adults, HDL cholesterol fell by up to 27 percent, SHBG fell in both sexes, total testosterone fell in men, LH and FSH fell in women, and eight participants had transient ALT rises, one withdrawn at 4.2 times the upper limit of normal (Dalton et al., 2011). In the breast cancer trial, 8 to 16 percent of women had grade 3 or 4 drug-related adverse events, most often raised liver transaminases, high blood calcium and fatigue (Palmieri et al., 2024).

Case reports describe biopsy-confirmed cholestatic liver injury in a man in his early 40s after two months of use (Bedi et al., 2021) and hepatocellular injury in a 31-year-old man three weeks after starting an enobosarm product (Weinblatt and Roy, 2022). In cardiac cells and rat hearts, ostarine raised fibrosis markers (in male but not female fibroblasts) and a cardiomyopathy marker (Leciejewska et al., 2023). Models: human trials, case reports, cells and rats.