LY305

Overview

LY305 is a nonsteroidal selective androgen receptor modulator (SARM) of the benzonitrile class, developed de novo by Eli Lilly and Company and engineered specifically for transdermal (gel) delivery. It is not a peptide — it is a small synthetic molecule (C14H17ClN2O, molecular weight 264.75 g/mol).

LY305 is a distinct compound from Lilly's LY2452473 / OPK-88004 (an enobosarm-like oral SARM). The two share a developer lineage but are different molecules and should not be conflated.

The design intent behind LY305 was to spare the liver and blood lipids: the molecule is deliberately cleared quickly by hepatic metabolism (limiting parent-compound exposure in the liver), and the transdermal route bypasses the gut-liver first-pass concentrations of an oral drug. In preclinical models it binds the androgen receptor with high affinity and behaves as a muscle-selective agonist. In a single Phase 1 study, a daily gel was well tolerated over four weeks in healthy volunteers.

Despite this favorable early profile, there is no evidence LY305 advanced beyond Phase 1, and there is no long-term human efficacy or safety data. It is an investigational research compound and is not an approved medicine anywhere.

[!WARNING] LY305 is not approved for human use anywhere and is not a "safer," "milder," or "legal" alternative to testosterone or anabolic steroids. Human data are limited to a single 4-week Phase 1 study. As a SARM it is prohibited in sport under WADA class S1.2. This page is a research-reagent reference and is not medical or legal advice (dated 2026-07-10).

Chemistry and structure

Mechanism of action

• Nonsteroidal SARM; high AR affinity. [In vitro] LY305 is a benzonitrile-class small molecule that binds the androgen receptor (AR) with high affinity, reported preclinical Ki ~2.03 nM, with strong agonist activity in C2C12 muscle cells (reported EC50 ~0.499 nM). Source: MedChemExpress/Probechem/MolNova reagent data; Krishnan et al. 2018.
• Tissue-selective (muscle vs prostate). [Animal] In orchidectomized rat models LY305 acted as an agonist in perineal (levator ani) muscle while behaving as only a weak partial agonist in the androgenic prostate — the tissue-selectivity that defines the SARM concept. Source: Krishnan et al., Andrology 2018.
• Selective for AR over other steroid receptors. [In vitro] Reported little-to-no affinity for glucocorticoid (GR), progesterone (PR) and mineralocorticoid (MR) receptors (Ki >800 nM). Source: reagent vendor summaries citing Krishnan et al. 2018.
• Engineered for transdermal delivery with high hepatic clearance. [Hypothesis] The molecule was deliberately designed to be highly cleared by hepatic metabolism, limiting parent-compound exposure in the liver; the transdermal (gel) route was chosen to avoid the high first-pass hepatic concentrations of an oral route. This design rationale is the stated basis for the observed lack of HDL suppression — a hypothesis supported by, but not definitively proven by, short Phase 1 data. Source: Krishnan et al. 2018; Kobidze et al. 2025.
• Extensively metabolized in vitro. [In vitro] A 2025 profiling study using human liver microsomes and S9 fraction identified 18 metabolites (9 Phase I via hydroxylation/dehydrogenation/oxidation; 9 Phase II via O-glucuronidation etc.), consistent with high hepatic clearance by design; a glucuronide (m/z 439) and a hydroxylated glucuronide (m/z 455) were proposed as doping-control targets. Source: Kobidze et al., Rapid Commun Mass Spectrom 2025.

Research and evidence

• Hypogonadism / male muscle and bone loss — Phase 1 completed; no evidence of Phase 2. [Human] A daily transdermal LY305 gel applied to the axilla/trunk for up to 4 weeks in 63 healthy volunteers (12 on placebo) showed dose-dependent serum exposure, was well tolerated with minimal adverse effects, and — unusually for a SARM — produced no statistically significant change in HDL cholesterol or hematocrit. Source: Krishnan et al., Andrology 2018;6(3):455-464.
• Skeletal muscle atrophy — preclinical. [Animal] In animal models of skeletal muscle atrophy, LY305 restored skeletal muscle mass through accelerated repair. Source: Krishnan et al. 2018.
• Bone / fracture healing — preclinical. [Animal] In a bone fracture model LY305 remained osteoprotective in the regenerating tissue and was void of deleterious effects on healing. Source: Krishnan et al. 2018.
• Anti-doping detection (analytical, not a therapeutic indication). [In vitro] The 2025 study published the first in-vitro metabolic profile of LY305 and proposed urinary glucuronide metabolites as doping-control markers; the authors note no adverse analytical finding for LY305 had been reported to date. Source: Kobidze et al. 2025.

Human data are limited to a single, short, small Phase 1 study. Everything else is preclinical (animal / in-vitro) or analytical.

Status and regulation

LY305 is an investigational research compound. It is not approved as a medicine by the FDA, EMA, or any other regulator, and there is no evidence of a completed Phase 2 program. No ClinicalTrials.gov Phase 2 record or official discontinuation notice was located, so whether development was formally discontinued or quietly halted is unknown.

Safety

• SARM-class hepatotoxicity / drug-induced liver injury (DILI). [Human] The SARM class is associated with drug-induced liver injury; the FDA has warned that unapproved SARM products can cause liver injury including cases of acute liver failure. This is a class/product signal from oral SARM products — not a finding specific to LY305. LY305 was explicitly designed (transdermal route plus high hepatic clearance) to reduce hepatic parent exposure, and its short Phase 1 study did not report hepatotoxicity. No long-term human liver-safety data for LY305 exist. Source: FDA warning on SARMs; NIH LiverTox.
• Testosterone / HPTA (HPG-axis) suppression. [Hypothesis] As an AR agonist, class-wide SARM effects include suppression of endogenous testosterone and gonadotropins (LH/FSH). LY305-specific endocrine-suppression data were not located for the 4-week Phase 1 study; treat HPTA suppression as an expected class risk rather than an established LY305 finding. Source: SARM class pharmacology.
• No HDL drop / no hematocrit change (LY305-specific). [Human] Unlike oral SARMs, the 4-week transdermal Phase 1 study reported no statistically significant change in HDL cholesterol or hematocrit. This is a short-duration, small-cohort finding in healthy volunteers and does not establish long-term cardiovascular or hematologic safety. Source: Krishnan et al. 2018.
• No human safety data beyond a single 4-week Phase 1 study. [Human] There is no Phase 2/3 data, no long-term exposure data, and no post-marketing surveillance. LY305 is not approved and has essentially no chronic-use human safety record. Source: development-status review.

Product contamination / mislabeling reality. [Human] A label reading "LY305" (or any SARM) is not a reliable statement of contents. In an analysis of 44 SARM products sold online, only 52% actually contained the labeled SARM, 39% contained a different unapproved drug, 9% contained no active drug at all, and the dose frequently differed from the label. Products sold as "research chemicals" carry unquantified identity, purity, and contamination risk. Source: Van Wagoner et al., JAMA 2017;318(20):2004-2010.

[!WARNING] There is essentially no chronic human safety record for LY305. SARM-class risks (liver injury, testosterone/HPTA suppression) should be assumed, and any product sold under this name may not contain what the label claims.

Legal status

Legal status is not assessed here and varies by country. In many jurisdictions SARMs are not approved for human use and may be restricted to laboratory/research use; supply for human consumption is frequently illegal. Separately from any national law, LY305 is prohibited in sport under the WADA Prohibited List class S1.2 (Other Anabolic Agents). This page does not provide legal advice (dated 2026-07-10).

How it compares

LY305 belongs to the nonsteroidal SARM family alongside compounds such as ostarine and testolone. Its distinguishing feature is the deliberate transdermal-gel design intended to spare the liver and lipids — the opposite delivery strategy from the orally dosed SARMs, which are more consistently associated with HDL suppression and hepatic exposure.

Common misconceptions

• "LY305 is a peptide." No. It is a small nonsteroidal benzonitrile molecule, not a peptide.
• "LY305 is the same as OPK-88004 / LY2452473." No. Those are a different (enobosarm-like oral) SARM; LY305 is a distinct transdermal molecule.
• "It's a proven, safer alternative to steroids." No. Human data are limited to a single 4-week Phase 1 study; there is no long-term efficacy or safety data, and it is not approved anywhere.
• "No HDL change means it's cardiovascularly safe." The no-HDL-change finding is short-term and small-cohort; it does not establish long-term cardiovascular safety.
• "A research-chem labeled LY305 contains LY305." Not reliably — most marketed SARM products are mislabeled or contaminated.