Andarine (S-4) – Kodiac biolabs

Our opinion on this compoundEstablished workhorse

26/100

Superseded prototype SARM with abandoned clinical development and narrow SAR probe utility

Yeah, andarine is historically important and practically irrelevant for most serious research programs right now. It’s the structural parent of the entire aryl propionamide SARM lineage, GTx-007, the compound Dalton’s group at the University of Tennessee used to establish the SARM concept before they handed the baton to ostarine and moved on. That lineage story is genuinely interesting. The compound itself is not.

Here’s the problem: andarine was superseded by its own derivative. Ostarine (enobosarm, GTx-024) exists specifically because S-4’s clinical development hit a wall in the form of that dose-dependent visual disturbance, the yellow-green color tint that appears around 50 mg and above. The mechanism appears to involve non-AR-mediated binding to retinal photoreceptor proteins, and while it reverses on discontinuation, it was clinically unacceptable for any chronic-use indication. GTx didnt abandon S-4 because the AR biology was wrong. They abandoned it because a structurally similar compound without the retinal liability was sitting in the pipeline. That’s not a research compound’s origin story you want to build a program around.

The SARM mechanism itself, tissue-selective AR partial agonism through the propionamide scaffold, is now mature pharmacology. The class has moved past andarine in every meaningful direction. Ostarine went to phase 3 in cancer cachexia and muscle wasting. LGD-4033 has published human PK data. RAD-140 has brain-penetrant properties that open a different set of questions entirely. Andarine is the structural ancestor of all of them, but ancestry doesn’t translate into research utility in 2026.

What we’d actually grant it: the retinal side effect is genuinely undercharacterized. The non-AR mechanism behind the photoreceptor binding is an open question, and if someone wanted to probe SARM off-target effects in visual tissue or build an in vitro assay for retinal safety screening in novel androgen modulators, S-4 is the natural tool. Thats a real research niche. The compound also has reference value in aryl propionamide SAR panels, where having the original scaffold in the comparison set makes mechanistic sense.

But those uses are narrow and specialized. The compound has thin preclinical depth outside the original Dalton program, essentially no clinical data of its own, and competes directly against ostarine in any application where you’d actually want an aryl propionamide SARM. For most research programs, andarine is a historical footnote kept in the library for completeness and lineage documentation. We dont expect it to drive a serious research agenda, and the score reflects that honestly.

Novelty: 22
Mechanism promise: 28
In-category differentiation: 20
Evidence quality: 30
Translational signal: 22
Research bench value: 45

Rationale Andarine scores low primarily because it was actively superseded by its own structural derivative (ostarine) and clinical development was abandoned due to retinal tolerability failure rather than mechanism failure; the aryl propionamide SARM mechanism is now decades-old pharmacology, and the compound has essentially no clinical data and limited research utility beyond SAR reference work and the undercharacterized photoreceptor side effect.

Selective androgen receptor modulator (early-generation)

An early-generation aryl propionamide SARM; the structural lineage compound from which ostarine was derived.

Abstract

Andarine (S-4, GTx-007; CAS 401900-40-1; molecular formula C19H18F3N3O6; molecular weight 441.36) is a non-steroidal aryl propionamide SARM developed by Dalton and colleagues at the University of Tennessee, the structural precursor to ostarine. The compound exhibits tissue-selective AR agonism and demonstrated efficacy in osteoporosis and BPH preclinical models. Notable for a dose-dependent visual side effect: yellow-green tint to vision at doses above approximately 50 mg, attributed to non-AR-mediated effects on retinal photoreceptors and pigments. The visual effect is reversible on discontinuation but proved clinically unacceptable for long-term development; GTx redirected development to ostarine for superior tolerability. Andarine retains research utility as the prototype aryl propionamide SARM and is widely used recreationally despite no regulatory approval. Plasma half-life is approximately 4 hours.

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-264Open 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.