Research Disclaimer: LGD-4033 is sold exclusively for in-vitro and laboratory research use. Not for unsupervised use. This content does not constitute medical advice.
LGD-4033 (ligandrol; originally Ligand Pharmaceuticals, licensed to Viking Therapeutics as VK5211) is a non-steroidal SARM with high AR binding affinity that has the most extensive human clinical trial dataset of any SARM. Phase 1 healthy volunteer trials and phase 2 hip fracture trials provide pharmacokinetic, pharmacodynamic, and safety data that make LGD-4033 the clinical reference SARM — the compound most often benchmarked against when interpreting SARM preclinical data. Its significant lean mass effects at milligram doses and well-characterized HPTA suppression profile make it central to research on tissue-selective AR agonism.
Table of Contents#
- Structure and AR Binding
- Pharmacokinetics: Human Data
- Phase 1 Clinical Trial Data
- Hip Fracture (VK5211) Phase 2 Data
- HPTA Suppression Profile
- LGD-4033 vs. RAD-140: Comparative Profile
- Research Protocols
- Key References
Structure and AR Binding#
LGD-4033 is a pyrrolidinyl-fluorobenzonitrile compound:
- Non-steroidal (no steroid ring backbone)
- Not a 5α-reductase substrate → no DHT equivalent
- Not aromatized → no estrogenic activity
- MW ~338 Da; high oral bioavailability
AR binding:
- Relative binding affinity: ~8–10× testosterone (Ki ~1–2 nM)
- Higher AR affinity than RAD-140 in some assays (varies by assay conditions)
- Less A:A selectivity than RAD-140 in Hershberger assay (~15–20:1 vs. RAD-140 ~90:1)
- Significantly more androgenic than RAD-140 at equivalent anabolic doses
Tissue selectivity mechanism: Same general SARM principle as RAD-140 — tissue-specific coactivator interaction — but with lower muscle:prostate selectivity ratio than RAD-140. LGD-4033's AR conformation is less selective at the coactivator interface.
Pharmacokinetics: Human Data#
From the Basaria et al. (2013) phase 1 trial — first published human SARM PK data:
| Parameter | Value (various doses) |
|---|---|
| Oral bioavailability | ~96% (very high; near-complete absorption) |
| t½ | ~24–36 hours |
| Tmax | ~1 hour |
| Protein binding | ~97% (primarily albumin) |
| Steady-state | ~7 days |
| Dose linearity | Linear PK across 0.1–1 mg doses |
| Metabolism | Hepatic (CYP3A4 minor; hydroxylation) |
| Elimination | Urine (primarily) |
Long t½ note: Like RAD-140, once-daily dosing maintains steady-state. Drug fully washes out within ~7–10 days after cessation.
Rodent PK (rat):
- t½ shorter: ~8–12h
- Once or twice daily oral gavage
- Standard rat dose: 0.1–3 mg/kg/day
Phase 1 Clinical Trial Data#
Basaria et al. (2013) — NEJM: Double-blind, placebo-controlled, dose-escalation study in 76 healthy male volunteers:
Doses studied: 0.1, 0.3, 1 mg/day × 21 days
Lean mass results:
| Dose | Lean mass change vs. placebo |
|---|---|
| 0.1 mg/day | +0.6 kg |
| 0.3 mg/day | +1.2 kg |
| 1 mg/day | +1.2 kg |
Lean mass increase in 21 days at just 1 mg/day — remarkable for a 21-day study with no change in diet or exercise.
Stair-climbing power:
- 1 mg/day group: significant improvement in stair-climbing speed and power (functional anabolic effect)
Adverse effects:
- HPTA suppression (dose-dependent; fully reversible by study end + 5 weeks)
- No significant liver enzyme elevations at 1 mg/day × 21 days
- Modest HDL-C decrease (~10–15%)
Hip Fracture (VK5211) Phase 2 Data#
Viking Therapeutics (VK5211 = LGD-4033) phase 2 in hip fracture patients:
- 243 hip fracture patients randomized to placebo, 0.5 mg/day, 1 mg/day, or 2 mg/day VK5211 × 12 weeks
Results:
- Lean body mass: +1.6 kg vs. placebo (2 mg group) at 12 weeks
- Appendicular lean mass: +0.9 kg
- Fat mass: slight decrease
- Physical performance: improved in some endpoints
This represents the most clinically relevant SARM dataset — demonstrating lean mass restoration in an elderly, injured population.
HPTA Suppression Profile#
LGD-4033 HPTA suppression from phase 1 data:
| Dose | LH change | FSH change | Testosterone change |
|---|---|---|---|
| 0.1 mg/day | -24% | -17% | -28% |
| 0.3 mg/day | -55% | -44% | -52% |
| 1 mg/day | -75% | -52% | -66% |
Complete HPTA recovery observed at 5 weeks after discontinuation of 21-day treatment.
Key observations:
- LH suppressed more than FSH (LH is more sensitive to AR-mediated feedback)
- Testosterone suppression is proportional to LH suppression (confirms intact Leydig cell function)
- Recovery within 5 weeks: faster than after equivalent-anabolic steroidal androgen doses
LGD-4033 vs. RAD-140: Comparative Profile#
| Property | LGD-4033 | RAD-140 |
|---|---|---|
| AR affinity | ~8–10× testosterone | ~7× testosterone |
| Hershberger A:A ratio | ~15–20:1 | ~90:1 |
| Oral bioavailability | ~96% | ~80% |
| t½ (human) | ~24–36h | ~60h |
| Human clinical data | Phase 1 + Phase 2 (most of any SARM) | Phase 1 |
| HPTA suppression | Dose-dependent; well-characterized | Dose-dependent |
| Neuroprotection data | Limited | Documented |
| Breast cancer indication | Not studied | Phase 1 (AR+ BC) |
| Research preference | Clinical benchmark SARM | Highest selectivity SARM |
Research Protocols#
Dose-response lean mass study (castrated rats)#
| Parameter | Specification |
|---|---|
| Model | Adult castrated male SD rats |
| Groups | 1. Vehicle, 2. TP 0.4 mg/kg SC (positive control), 3–6. LGD-4033 0.01, 0.1, 0.3, 1 mg/kg oral daily |
| Duration | 28 days |
| Endpoints | Body composition (DEXA), levator ani and ventral prostate weights (A:A ratio), serum LH/FSH/testosterone, protein synthesis (SUnSET) |
Frailty/sarcopenia model (aged rats)#
| Parameter | Specification |
|---|---|
| Model | 24-month-old male SD rats (aged sarcopenic model) |
| Groups | 1. Vehicle, 2. LGD-4033 0.1 mg/kg/day oral, 3. Testosterone enanthate 3 mg/kg SC q3d |
| Duration | 12 weeks |
| Endpoints | Lean mass (DEXA), grip strength, wire hang test, soleus/EDL fiber cross-sectional area (histology), mitochondrial function (citrate synthase activity) |
Key References#
-
Basaria S, et al. (2013). "The safety, pharmacokinetics, and effects of LGD-4033 on muscle and bone." Journals of Gerontology: Series A, 68(1):87–95.
-
Dalton JT. (2014). "Androgen receptor structure, function and biology." In: Principles of Andrology.
-
Solomon ZJ, et al. (2019). "Selective androgen receptor modulators: current knowledge and clinical applications." Sexual Medicine Reviews, 7(1):84–94.
Research Use Only: LGD-4033 is sold exclusively for in-vitro research and laboratory use. Not for unsupervised use. JuicedPharma does not provide medical advice.
Published by JuicedPharma Research Team · September 2026 · Category: Research Protocols & Science
