Overview

GSK-2849466 is a non-steroidal selective androgen receptor modulator (SARM) developed by GlaxoSmithKline as part of their pipeline targeting androgen-related conditions such as sarcopenia, cachexia, and functional limitations associated with aging or chronic disease. Like other SARMs, GSK-2849466 was designed to selectively activate androgen receptors in muscle and bone tissue while avoiding the undesirable androgenic effects on the prostate and sebaceous glands that characterize traditional anabolic steroids.

Preclinical data for GSK-2849466 demonstrated tissue-selective anabolic activity in animal models, with favorable separation between myotropic (muscle-building) and androgenic effects. The compound was evaluated in early-phase clinical studies to characterize its pharmacokinetic profile, safety, and tolerability in human subjects. As with many pharmaceutical SARMs in development, the primary therapeutic goal was to address the significant unmet need for safe and effective anabolic therapies in populations vulnerable to muscle loss, including the elderly, cancer patients, and those with chronic obstructive pulmonary disease.

GSK-2849466 is part of a broader class of investigational SARMs that includes GSK-2881078, GSK-971086, GLPG-0492, and RAD-140. Each compound in this class has a unique pharmacological profile in terms of potency, selectivity, and oral bioavailability. The clinical development status of GSK-2849466 should be verified through current literature, as GlaxoSmithKline's SARM pipeline has undergone various prioritization changes over time.

Mechanism of Action

GSK-2849466 is a selective androgen receptor modulator (SARM) developed by GlaxoSmithKline, though its development was subsequently discontinued. Like all SARMs, its mechanism centers on tissue-selective activation of the androgen receptor (AR), a nuclear receptor transcription factor that mediates the biological effects of androgens.

Upon binding to the AR in the cytoplasm, GSK-2849466 induces a specific conformational change in the receptor that differs from those induced by natural androgens like testosterone or DHT. This triggers dissociation of heat shock proteins (HSP90, HSP70), receptor dimerization, and translocation of the ligand-receptor complex into the nucleus. In the nucleus, the complex binds to androgen response elements (AREs) in the promoter regions of target genes and modulates their transcription.

The tissue selectivity of GSK-2849466 arises from the differential recruitment of co-regulatory proteins determined by the SARM-induced AR conformation. In anabolic tissues such as skeletal muscle and bone, the AR conformation preferentially recruits co-activator proteins, driving robust transcription of genes involved in protein synthesis and cell growth. In androgenic tissues such as the prostate and seminal vesicles, the same conformation leads to weak co-activator recruitment or co-repressor binding, resulting in minimal androgenic stimulation. Unlike testosterone, SARMs like GSK-2849466 are not substrates for 5α-reductase or aromatase, preventing conversion to the more potent DHT or to estrogens, which further reduces off-target effects.

Reconstitution Calculator

Research

Safety Profile

Safety Profile: GSK-2849466

Common Side Effects

• Limited publicly available clinical data; this compound is an investigational drug from GlaxoSmithKline
• Based on early-phase trial reports: headache, fatigue, and mild nausea
• Injection site reactions (if administered parenterally): redness, pain, swelling
• Mild transaminase elevations (ALT/AST)
• Musculoskeletal discomfort

Serious Adverse Effects

• Hepatotoxicity: As with many investigational small molecules, liver enzyme elevation is a primary safety signal to monitor
• Cardiovascular effects: Changes in blood pressure or heart rate may occur; long-term cardiovascular risk profile unknown
• Hormonal disruption: Depending on mechanism of action, potential for endocrine-related adverse events
• Immunogenicity: If biologic or peptide-based, anti-drug antibodies may develop
• Unknown long-term toxicity: As an investigational agent, chronic safety data are unavailable

Contraindications

• Known hypersensitivity to GSK-2849466 or any formulation excipient
• Severe hepatic impairment (Child-Pugh C) unless part of a supervised clinical trial
• Pregnancy and lactation (teratogenic risk unknown; assume risk until proven otherwise)
• Women of childbearing potential not using adequate contraception
• Concurrent enrollment in another investigational drug study (unless protocol-permitted)

Drug Interactions

• CYP450 enzyme interactions: Specific CYP profile not fully characterized; exercise caution with strong CYP3A4 inhibitors or inducers
• Hepatotoxic agents: Avoid concurrent use with known hepatotoxic drugs to reduce additive liver injury risk
• P-glycoprotein substrates: Potential for drug transporter interactions; not fully elucidated
• QT-prolonging drugs: Until cardiac safety is fully characterized, avoid co-administration with drugs known to prolong QT interval
• Immunosuppressants: Interaction potential unknown; use with caution

Population-Specific Considerations

• Pregnancy/Lactation: Contraindicated; no reproductive toxicology data available. Women of childbearing potential must use effective contraception during and after treatment
• Pediatric: Not studied in children; use only within approved clinical trial protocols
• Elderly: Pharmacokinetics may be altered; dose adjustment guidance not yet established
• Hepatic impairment: Likely requires dose adjustment or exclusion; monitor LFTs closely
• Renal impairment: Insufficient data; use with caution and monitor renal function
• Note: This compound is investigational. All safety information is preliminary and subject to revision as clinical data mature

Pharmacokinetic Profile