Ligandrol (LGD-4033) – Kodiac biolabs

Our opinion on this compoundEstablished, active research

39/100

Canonical high-affinity SARM with real phase 1 data, but mechanistically mature and clinically stalled

Look, there’s a version of this compound that sounds exciting on paper: sub-nanomolar AR affinity, tissue selectivity, phase 1 lean-mass data, and a development history at two serious pharmaceutical shops. That version isn’t wrong. But we’re scoring research merit in 2026, and the honest picture of LGD-4033 is a mature SARM with a mostly settled mechanism in a class that has been chasing the same tissue-selectivity promise for twenty years without a single approved drug to show for it.

The mechanism itself, tissue-selective androgen receptor agonism via a non-steroidal ligand, is real and reasonably well understood. LGD-4033 binds AR at roughly 1 nM (Ki), several-fold tighter than ostarine, and that affinity advantage is why it became the canonical reference compound for high-affinity SARM work. If your research question is specifically about the pharmacology of high-affinity partial AR agonism, theres a legitimate reason to reach for this molecule. That single-axis differentiation is real and we credit it in the bench value and differentiation scores. But it doesn’t change the fact that the mechanism hasn’t evolved, its single-receptor agonism in a class that has been around long enough that Ligand Pharmaceuticals itself spun the asset out to Viking Therapeutics to pursue it further.

The clinical story is complicated. The Bhasin phase 1 data (0.1-1 mg, 21 days, healthy males) is genuinely clean: dose-dependent lean body mass gains, no significant prostate signal, reasonable tolerability. Thats a real signal. The problem is what came after. The VK5211 hip fracture program has had intermittent readouts and hasn’t generated the sort of decisive phase 2 data that would make this compound compelling to follow right now. HPG axis suppression at the higher dose tier is a liability the class has never fully escaped, and recreational use at 5-10 mg (supratherapeutic by clinical standards) has muddied the human data pool considerably.

What we like: the canonical status matters. LGD-4033 is the molecule you’d reach for if you need a high-affinity SARM probe to interrogate AR-dependent pathways in vitro or in a clean animal model. The pharmacokinetics (24-36 hour half-life) are researcher-friendly. The phase 1 dataset is honest and reproducible. What we don’t like: the class promise has underdelivered for two decades, the VK5211 program hasn’t produced a decisive signal, and there’s genuinely nothing novel happening mechanistically. If you’re not specifically studying SARMs, there’s little here that you can’t get from a better-characterized or more clinically advanced tool. Score it accordingly: useful in the right context, not a priority pick outside of it.

Novelty: 28
Mechanism promise: 30
In-category differentiation: 45
Evidence quality: 45
Translational signal: 42
Research bench value: 58

Rationale LGD-4033 scores modestly on novelty and mechanism because selective AR agonism is a mature, well-trodden strategy, but its canonical status as the reference high-affinity SARM and solid phase 1 lean-mass data keep it out of the workhorse or established-mature basement. The intermittent phase 2 (VK5211) trajectory and HPG suppression signal cap the translational score.

Selective androgen receptor modulator

A non-steroidal SARM developed for muscle wasting; one of the more potent SARMs at AR binding.

Abstract

Ligandrol (LGD-4033, VK5211; CAS 1165910-22-4; molecular formula C14H12F6N2O; molecular weight 338.25) is a non-steroidal SARM developed by Ligand Pharmaceuticals (later out-licensed to Viking Therapeutics as VK5211). The compound is a high-affinity AR ligand (Ki approximately 1 nM, several-fold higher affinity than ostarine) with tissue-selective agonism similar to other SARMs. Phase 1 trials in healthy male volunteers demonstrated dose-dependent increases in lean body mass at doses of 0.1 to 1 mg daily over 21 days, with no significant prostate effects but with HPG axis suppression at the higher dose tier. Subsequent phase 2 development (VK5211) targeted hip fracture recovery; results have been intermittent. Plasma half-life is approximately 24 to 36 hours. The compound is widely used recreationally at supratherapeutic doses (5 to 10 mg) and is banned by WADA. Used as the canonical high-affinity SARM in mechanism studies.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

KDC-MN-262Open in new tab →

Download PDF →

FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.