Enobosarm: Molecular Structure

Molecular Structure#

Enobosarm (Ostarine, GTx-024, MK-2866) is a nonsteroidal selective androgen receptor modulator belonging to the aryl propionamide class of SARMs. Unlike the peptide therapies that comprise most of this site's content, enobosarm is a synthetic small molecule that is orally bioavailable and does not require injection.

The molecule was designed to bind the androgen receptor (AR) ligand-binding domain with high affinity while inducing a conformational change in the receptor that differs from that induced by testosterone. This conformational difference leads to differential recruitment of coregulator proteins in different tissues, which is the molecular basis for tissue selectivity.

Chemical Name#

(2S)-3-(4-cyanophenoxy)-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide

Key Structural Features#

1. Trifluoromethyl group: Enhances metabolic stability and AR binding affinity
2. Two cyano (nitrile) groups: On both the aniline and phenoxy rings, contributing to AR binding
3. Chiral center: The (S)-configuration at the propionamide center is critical for biological activity
4. Hydroxyl group: Participates in hydrogen bonding within the AR ligand-binding pocket
5. No steroid backbone: Fundamentally different from testosterone, enabling tissue selectivity

Chemical Properties#

Pharmacokinetics#

Enobosarm has favorable pharmacokinetic properties for an oral medication:

• Oral bioavailability: Sufficient for therapeutic exposure via oral route
• Half-life: Approximately 24 hours, supporting once-daily dosing
• Metabolism: Hepatic metabolism (CYP-mediated); ALT elevations observed in some patients suggest hepatic burden
• Protein binding: Not fully characterized publicly
• Steady state: Achieved within approximately 5 days of daily dosing based on the ~24-hour half-life

Pharmacodynamics#

• AR binding affinity: High affinity for the androgen receptor ligand-binding domain
• Tissue selectivity ratio: Anabolic activity in muscle/bone with reduced androgenic activity in prostate/sebaceous glands
• Onset: Lean mass changes detectable within 12 weeks in clinical trials
• Dose response: Dose-dependent increases in lean body mass at 1 mg and 3 mg

Comparison with Related Molecules#

Mechanism of Tissue Selectivity#

The tissue selectivity of enobosarm is mediated by differential coregulator recruitment:

1. In muscle: The AR-enobosarm complex recruits coactivators (SRC-1, p300) that drive anabolic gene expression, promoting muscle protein synthesis
2. In prostate: The AR-enobosarm complex has reduced ability to recruit the same coactivators, resulting in minimal prostatic stimulation
3. In bone: Intermediate coactivator recruitment promotes osteoblast activity and bone preservation

This mechanism differs from 5-alpha reductase inhibitor approaches, which reduce DHT in prostate but do not achieve the same degree of tissue selectivity for muscle.

Stability#

As a small molecule:

• Chemically stable at room temperature
• Does not require refrigeration or cold chain storage
• No reconstitution needed
• Significantly simpler handling than peptide therapeutics

Related Reading#

• Enobosarm overview and research guide
• Peptides similar to enobosarm
• Enobosarm research evidence