SARMs are non-steroidal small-molecule AR ligands designed to dissociate anabolic effects in muscle + bone from androgenic effects in prostate + sebaceous glands + scalp. Mechanism: tissue-specific coactivator/corepressor recruitment to ligand-bound AR — analogous to SERMs at ER. Phase I-II clinical data show muscle mass + bone density gains, but every late-stage trial has failed (cardiovascular signal, hepatotoxicity, fertility suppression). All SARMs in this pathway are research-only — none are FDA-approved despite open supplement-market distribution as "lifestyle" hormone modulators. WADA + military prohibited. Sometimes-confused-with: bicalutamide / enzalutamide (covered in aromatase_androgen_receptor_axis) are AR antagonists for prostate cancer — opposite mechanism.
Organ Systems
endocrine
musculoskeletal
Pathway Steps
sarm-binding → tissue-selective-ar-activation — via AR ligand binding → tissue-specific coactivator recruitment (no enzymatic conversion to DHT or aromatization). Selective androgen receptor modulators (SARMs) bind the androgen receptor but induce tissue-selective conformations, aiming for anabolic effects in muscle and bone with less prostate/virilizing activity than testosterone. Investigated for muscle-wasting (and widely abused in sport), none is yet approved, and liver and cardiovascular safety remain concerns.
Known Modulators
lgd 4033 (activator) — AR (anabolic-selective, oral). ligandrol; most-distributed SARM; phase I data on muscle/bone; suppresses HPG; not FDA-approved
ostarine (activator) — AR (anabolic-selective). MK-2866 enobosarm; failed phase 3 cancer cachexia trial; widely abused; WADA-banned
rad 140 (activator) — AR (anabolic, neuroprotective claim). testolone; potent AR agonist; hepatotoxicity reports; not approved
yk 11 (activator) — AR + myostatin pathway modulation. unique SARM with myostatin-inhibitor claim; structurally a 5α-DHT analog
s 23 (activator) — AR (anabolic with male contraceptive claim). reversibly suppresses spermatogenesis in animals; not human-tested
andarine (activator) — AR (anabolic-selective). S-4; original SARM; vision side effect (yellow tint) at higher doses
cardarine (activator) — PPAR-δ (not actually AR — misclassified as SARM). GW501516; PPAR-δ agonist; halted for carcinogenicity in 5/6 organs in rodent studies
stenabolic (activator) — Rev-erb-α (not AR — circadian). SR9009; Rev-erb agonist; metabolic + circadian effects; not actually a SARM but bundled with them in research-supplement market
lgd 3303 (activator) — AR (anabolic with osteoporosis claim). related to LGD-4033; less-studied; research-only
acp 105 (activator) — AR (anabolic, lower androgenic ratio). research SARM
rad 150 (activator) — AR (TLB-150, testolone ester). testolone ester research compound