Ostarine vs LGD-4033: Research Comparison of MK-2866 and Ligandrol
Ostarine (MK-2866) and LGD-4033 (Ligandrol) are the two most extensively characterised selective androgen receptor modulators (SARMs) in the published scientific literature. Both were developed as investigational drugs targeting muscle wasting and bone density loss, both have completed Phase I and Phase II clinical trials, and both are widely used as reference compounds in androgen receptor research. Despite their shared mechanistic class, they differ significantly in receptor binding affinity, tissue selectivity ratios, pharmacokinetic profiles, and the depth of clinical data available.
This comparison is intended for researchers selecting between these compounds for laboratory or pre-clinical work. Neither compound is approved for human use by the TGA or equivalent regulatory bodies.
Development Background
MK-2866 (Ostarine / Enobosarm) was developed by GTx, Inc. as part of a programme to identify non-steroidal AR ligands for treating cancer cachexia, muscle wasting, and osteoporosis. It was the first SARM to complete Phase II clinical trials — the ENOBOSARM-1 and ENOBOSARM-2 trials in non-small cell lung cancer patients — and has the most comprehensive published dataset of any compound in its class.
LGD-4033 (Ligandrol / VK5211)Â was developed by Ligand Pharmaceuticals and licensed to Viking Therapeutics. Designed as a more potent AR agonist with higher binding affinity as a primary design goal. Phase I dose-escalation studies in healthy volunteers were completed, and Phase II trials (VK5211 in hip fracture recovery) have been conducted. Its clinical dataset is less extensive than MK-2866's but includes robust human pharmacokinetic data.
Structural Class
MK-2866 belongs to the arylpropionamide class; LGD-4033 belongs to the tetrahydroquinoline class. These structural differences produce distinct receptor binding geometries, different AR conformational changes upon binding, and consequently different tissue selectivity profiles — the structural basis for the pharmacological differences described below.
Androgen Receptor Binding Affinity
CompoundAR Binding KiRelative to DHTDHT (reference)~0.1 nM1.0× (reference)LGD-4033~1.0 nM~0.1× DHTMK-2866~3.8 nM~0.026× DHTTestosterone~1–3 nM~0.05–0.1× DHT
LGD-4033 binds the AR with approximately 3.8-fold higher affinity than MK-2866 (Ki ~1.0 nM vs ~3.8 nM). This translates to greater receptor occupancy at equivalent molar concentrations and contributes to LGD-4033's more potent anabolic effects per mole in pre-clinical models.
Tissue Selectivity: Anabolic-to-Androgenic Ratio
In the orchidectomised rat model (standard pre-clinical selectivity assessment):
MK-2866: Levator ani ED50 = 0.03 mg/day; Prostate ED50 = 0.12 mg/day → A:A ratio ~4:1
LGD-4033: Levator ani ED50 = ~0.006–0.010 mg/day; Prostate ED50 = ~0.021 mg/day → A:A ratio ~2–3:1
LGD-4033 is more potent in absolute terms (lower ED50 in both tissues), but MK-2866's A:A selectivity ratio is higher. For research where androgenic side effects are a confounder (prostate stimulation in animal models), MK-2866's higher selectivity ratio may be preferable. For research requiring maximum anabolic stimulus per dose, LGD-4033's higher potency is advantageous.
Pharmacokinetics: Direct Comparison
ParameterMK-2866 (Ostarine)LGD-4033 (Ligandrol)Human t½ (oral)24–36 hours24–36 hoursRat t½ (IV)~6 hours~5 hoursOral bioavailability>80% (estimated)>80% (estimated)Linear kineticsYes (Phase I confirmed)Yes (Phase I confirmed)Steady-state (daily)~5–7 days~5–7 days
The pharmacokinetic profiles are strikingly similar in humans — both exhibit ~24–36 hour half-lives, high oral bioavailability, and linear kinetics. For comparative research protocols, dosing intervals and washout periods can be kept consistent between compounds, simplifying experimental design.
Clinical Data Comparison
MK-2866Â has the larger clinical dataset: Phase II ENOBOSARM trials at 3 mg/day for 116 days in cancer patients produced statistically significant lean body mass gains and functional improvements vs placebo. Adverse event profile was favourable. This is the longest treatment duration and largest clinical population of any SARM studied.
LGD-4033 Phase I (1 mg/day × 21 days in healthy volunteers) showed statistically significant lean body mass increases even at the lowest dose — demonstrating high potency. Dose-dependent HPG axis suppression (testosterone and SHBG reduction) was observed, returning to baseline within 5 weeks. Phase II (VK5211, hip fracture recovery, 2 mg/day × 12 weeks) showed lean body mass and strength improvements.
HPG Axis Suppression
Both compounds suppress the hypothalamic-pituitary-gonadal axis, but LGD-4033 produces more pronounced suppression per milligram. At 1 mg/day in Phase I, LGD-4033 produced measurable testosterone and SHBG reduction. MK-2866 at 3 mg/day in Phase II produced modest HPG effects, less pronounced than testosterone equivalents.
For research requiring minimal HPG interference, MK-2866's lower suppression per anabolic dose is preferable. For HPG feedback mechanism research via SARM-mediated AR activation, LGD-4033's more potent suppression provides a cleaner signal.
Research Application Guide
Research ApplicationPreferred CompoundRationaleAR binding assays (reference standard)MK-2866Largest published comparative datasetMaximum anabolic stimulusLGD-4033~4× higher AR affinity; lower ED50Tissue selectivity studiesMK-2866Higher A:A ratio (~4:1 vs ~2–3:1)HPG axis suppression modellingLGD-4033More potent HPG suppression at lower dosesLong-duration protocolsMK-2866116-day clinical data; best-characterised long-term profile
Summary
Binding affinity: LGD-4033 binds AR ~4× more tightly than MK-2866
Potency:Â LGD-4033 is more potent (lower ED50) in both anabolic and androgenic tissue
Selectivity ratio: MK-2866 shows higher anabolic-to-androgenic selectivity (~4:1 vs ~2–3:1)
Pharmacokinetics: Nearly identical — both ~24–36 hour human half-life
Clinical data:Â MK-2866 has a substantially larger dataset (116-day Phase II)
HPG suppression:Â LGD-4033 produces greater suppression per milligram
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