OPK-88004 is an investigational oral selective androgen receptor modulator (SARM): a non-steroidal drug designed to activate the androgen receptor in muscle and bone while having less effect on the prostate. Eli Lilly discovered it under the code LY2452473. Transition Therapeutics licensed it in 2015 (as TT701), and OPKO Health took it over when it bought Transition in 2016 and renamed it OPK-88004.
It has been tested in three published or registered phase 2 trials: in men with erectile dysfunction, in testosterone-deficient prostate cancer survivors, and in men with benign prostatic hyperplasia (BPH). The single most important fact: it has never been approved anywhere. The last trial was stopped by its sponsor in 2019, and no newer trial is registered.
This page summarizes what the trial registry records, the published trials and company filings report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Non-steroidal SARM (tetrahydrocyclopenta[b]indole, an indole-type structure) |
| Code names | LY2452473 (Eli Lilly), TT701 (Transition Therapeutics), OPK-88004 / OPK88004 (OPKO Health) |
| Route | Oral, once daily |
| Doses studied in trials | 1, 5, 15 and 25 mg/day for 12–16 weeks |
| Half-life | ≈27 h for the parent drug after a single 15 mg dose in 6 healthy men |
| Main metabolism | Liver metabolism; CYP3A4 the largest contributor in lab tests |
| Development stage | Phase 2; BPH trial terminated by sponsor in 2019 |
| US status | Not FDA-approved; not listed as a Schedule III anabolic steroid |
| WADA status | Prohibited at all times (S1.2, SARMs) |
What it is
LY2452473 is a small non-steroidal molecule. PubChem lists its formula as C₂₂H₂₂N₄O₂, molecular weight 374.4 g/mol, and its chemical name as propan-2-yl N-[(2S)-7-cyano-4-(pyridin-2-ylmethyl)-2,3-dihydro-1H-cyclopenta[b]indol-2-yl]carbamate (PubChem CID 24963749). Doping-control chemists group it with GSK2881078 as an “indole” SARM, a different chemical family from ostarine-type arylpropionamides (Stacchini et al., J Pharm Biomed Anal 2021).
The compound belongs to a Lilly patent on tetrahydrocyclopenta[b]indole androgen receptor modulators, filed in 2007 and granted in 2011 (US 7,968,587). Lilly and UCLA chemists later published how the key ring-forming step of its manufacture works, describing LY2452473 as a candidate treatment for side effects of prostate cancer therapies (Noey et al., J Org Chem 2017).
Are OPK-88004 and LY2452473 the same compound?
Yes. Primary documents link the two names directly:
| Evidence | What it shows |
|---|---|
| Lilly–Transition license agreement, filed with the SEC in May 2015 | Defines the licensed “Lead Compound” as Lilly SARM compound LY2452473 (license agreement) |
| Transition press release, May 6, 2015 | Announces the same Lilly SARM in-license under the name TT701 (Transition release) |
| OPKO 10-K for 2016 vs 10-K for 2025 | Both state that U.S. Patent 7,968,587, licensed from Lilly, covers the SARM: called TT701 in the 2016 report and OPK88004 in the 2025 report (OPKO 10-K 2016; OPKO 10-K 2025) |
| Trial NCT02499497 | Registered with LY2452473 as the study drug (ClinicalTrials.gov); its published reports name the drug OPK-88004 and cite the same registration number (Guo et al., J Endocr Soc 2022) |
PubChem also resolves both names to the same record (CID 24963749).
Mechanism
Like other SARMs, OPK-88004 binds the androgen receptor. The trial registry describes it as an agonist (activator) in muscle that spares the prostate (NCT02499497). The claims of prostate-sparing and anti-prostate effects come from animal work the sponsor provided as unpublished data. That work reported muscle and bone effects without prostate effects in castrated mice, and prostate shrinkage in dogs (Pencina et al., JCEM 2021). These animal findings have not been shown to translate to people; the human trials below are the relevant evidence.
Pharmacokinetics
The only published human pharmacokinetic study gave a single 15 mg radiolabeled oral dose to 6 healthy men (Yi et al., Drug Metab Dispos 2012):
| Parameter | Result |
|---|---|
| Time to peak plasma level | 2–3 h |
| Terminal half-life, parent drug | 27 h |
| Terminal half-life, total drug-related material | 51 h |
| Share of plasma exposure as parent drug | ≈42% (two metabolites made up ≈21% and ≈35%) |
| Excretion of the dose by 312 h | 47.9% in urine, 46.6% in feces |
| Main enzyme | CYP3A4 (in vitro phenotyping) |
Very little unchanged drug appeared in urine or feces, so the body clears it mainly by metabolism. No single pathway accounted for more than 30% of the dose. Because CYP3A4 was the largest contributor in lab tests, drugs that block or induce CYP3A4 could in principle change exposure, but no interaction study has been published.
Regulatory status
- Not approved. In 2015 the trial registry stated that the FDA has not approved LY2452473 for any disease (NCT02499497). No approval has followed.
- Development stalled. OPKO’s phase 2 BPH trial was “terminated by sponsor decision” in 2019 (NCT03297398). OPKO’s annual report filed in February 2026 mentions OPK88004 only in its patent section, noting the compound patent expires in November 2027 (OPKO 10-K 2025).
- Not a named controlled substance in the US. It is not among the anabolic steroids listed in Schedule III (21 CFR 1308.13).
- Banned in sport. WADA prohibits SARMs at all times, in and out of competition, under S1.2 “Other anabolic agents” (WADA 2026 Prohibited List).
What the research shows
All human efficacy data come from three 12–16 week phase 2 trials in middle-aged and older men. No trial has studied women, young healthy men, or treatment longer than 16 weeks.
Prostate cancer survivors (SARM-PC trial)
This double-blind trial randomized 114 testosterone-deficient men (mean age 67.5) who had had their prostate removed for low-grade cancer and had undetectable PSA for at least 2 years (Pencina et al., JCEM 2021). They took placebo or 1, 5 or 15 mg OPK-88004 daily for 12 weeks. Randomization was staged for safety: the 15 mg arm was added, and the 1 mg arm dropped, only after the first 50 participants showed no PSA recurrence, so the 15 mg arm had just 14 men.
Body composition by DXA scan, from the registry results (NCT02499497):
| Arm (n started) | Total lean mass change | Appendicular lean mass change | Total fat mass change |
|---|---|---|---|
| Placebo (36) | +0.20 kg | −0.04 kg | −0.05 kg |
| 1 mg (28) | +0.33 kg | +0.15 kg | −0.52 kg |
| 5 mg (36) | +1.48 kg | +0.80 kg | −0.75 kg |
| 15 mg (14) | +1.92 kg | +1.05 kg | −0.86 kg |
In the paper’s model, lean mass rose by 1.5 kg (95% CI 1.0–2.0) on 5 mg vs 0.3 kg (95% CI −0.3–0.8) on placebo, and the lean-mass increase was dose-related (p under 0.001). Percent body fat fell by 1.1% on 5 mg vs 0.1% on placebo.
What did not improve:
- Sexual function. The primary outcome, sexual activity, did not differ among groups, nor did sexual desire or erectile function.
- Physical performance. Leg-press strength, stair-climb power and walking speed did not differ significantly among arms (all p values over 0.2).
- Mood, fatigue and bone turnover markers did not differ either.
No participant had a PSA recurrence. The authors noted the trial was too short and too small to assess the risk of cancer recurrence, and that the results should not be extended to men with higher-grade cancer.
Benign prostatic hyperplasia (OPKO trial, terminated)
OPKO’s phase 2 trial randomized 114 men with BPH (mean age 64.6) to placebo, 15 mg or 25 mg OPK-88004 daily for 16 weeks (NCT03297398). The sponsor terminated it, and results were posted to the registry but not published in a journal.
| Outcome at week 16 | Placebo (n=36) | 15 mg (n=40) | 25 mg (n=38) |
|---|---|---|---|
| PSA change (primary outcome) | −3.0% | −1.5% | −15.4% |
| Lean body mass change | +0.04 kg | +1.61 kg | +1.96 kg |
| Fat mass change | −0.20 kg | −1.47 kg | −1.49 kg |
| Completed the study | 28 | 23 | 23 |
| Stopped because of an adverse event | 1 | 4 | 4 |
The registry posts no statistical test for the primary outcome. Urinary flow rate and symptom scores did not show a consistent benefit over placebo.
Erectile dysfunction (Lilly trial)
Lilly’s 12-week phase 2 trial randomized 410 men (mean age 59.9) whose erectile dysfunction responded incompletely to PDE5 inhibitors (drugs such as tadalafil) (NCT01160289). Results were posted to the registry only:
| Arm | n | Change in erectile function score (IIEF-EF) | HDL cholesterol change |
|---|---|---|---|
| LY2452473 1 mg + tadalafil 5 mg | 85 | +2.5 | −7.4% |
| LY2452473 5 mg + tadalafil 5 mg | 97 | +2.4 | −17.0% |
| LY2452473 5 mg alone | 52 | −1.0 | −22.2% |
| Tadalafil 10 mg | 89 | +3.5 | +1.8% |
| Tadalafil 5 mg | 87 | +2.1 | +1.6% |
Adding LY2452473 to tadalafil 5 mg did not improve erectile function over tadalafil 5 mg alone (p = 0.50 and p = 0.498). Only 31 of 52 men in the LY2452473-alone arm completed the trial, compared with 80 of 89 and 73 of 87 in the tadalafil-only arms. When licensing the drug, Transition said a completed 12-week Lilly phase 2 study of 350 men had shown significant gains in lean body mass and a strength measure (Transition release). It did not name the trial, and those body-composition results have not been published or posted.
Side effects and risks
The total human exposure is small: a few hundred men treated for 12–16 weeks. Long-term safety, cardiovascular outcomes and effects in women are unknown.
HDL cholesterol
HDL (“good”) cholesterol fell with dose in every trial, as it does with other oral SARMs and oral androgens. In the prostate cancer survivor trial (Pencina et al., JCEM 2021):
| Arm | HDL change (95% CI) |
|---|---|
| Placebo | −2.4 mg/dL (−4.4 to −0.4) |
| 1 mg | −5.5 mg/dL (−7.8 to −3.2) |
| 5 mg | −13.5 mg/dL (−15.4 to −11.6) |
| 15 mg | −18.4 mg/dL (−21.5 to −15.4) |
LDL and total cholesterol did not change significantly. A follow-up analysis of the same trial found that the drug suppressed HDL cholesterol and its main protein, APOA1, and raised hepatic lipase. HDL particle size and cholesterol efflux capacity (a lab measure of how well HDL removes cholesterol from cells) changed little (Guo et al., J Endocr Soc 2022). The authors concluded that the HDL drop is not necessarily harmful but that only outcome trials could settle the question.
Hormone suppression
OPK-88004 lowered SHBG (sex hormone-binding globulin, which carries testosterone in the blood), total testosterone and estradiol in a dose-related way (Pencina et al., JCEM 2021):
| Arm | Total testosterone | SHBG | Free testosterone |
|---|---|---|---|
| Placebo | −2.9 ng/dL | −2.4 nmol/L | +1.9 pg/mL |
| 1 mg | −91.2 ng/dL | −12.3 nmol/L | +6.9 pg/mL |
| 5 mg | −165.1 ng/dL | −22.7 nmol/L | +15.1 pg/mL |
| 15 mg | −178.4 ng/dL | −25.4 nmol/L | +17.9 pg/mL |
Free testosterone rose in that trial, but the authors list suppression of the men’s own testosterone among possible reasons sexual function did not improve. In the BPH trial, “blood testosterone decreased” was reported as an adverse event in 7 of 40 men on 15 mg and 5 of 38 on 25 mg vs none on placebo, and decreased sperm concentration in 1 and 3 men vs none (NCT03297398).
Liver, blood and other findings
- Liver enzymes. One man on 15 mg in the prostate cancer trial had AST and ALT above the normal limit, which returned to baseline after stopping. In the BPH trial, transaminase, ALT or AST increases were reported in a few men in each drug arm and in 1 man on placebo.
- Blood counts. Hemoglobin and hematocrit (the share of blood made up of red cells) rose slightly relative to placebo. No participant developed erythrocytosis (abnormally high red cell levels). Platelet counts rose with dose.
- Serious events. In the prostate cancer trial, the authors judged none of the three serious adverse events drug-related. In the BPH trial, 2 men on 25 mg had serious events (coronary artery disease; bile duct obstruction with cholangitis), and none on placebo. In the Lilly erectile dysfunction trial, the registry lists one cardiac arrest and one death in the 5 mg-alone arm (52 men). The registries do not state whether these were caused by the drug.
Legal status and use outside medicine
Because it was never approved, any product sold as OPK-88004 or LY2452473 is outside the regulated drug supply, and its content and purity are unverified. Anti-doping laboratories have built tests for it in human urine (Stacchini et al., J Pharm Biomed Anal 2021). In horses, a single oral dose produced 15 metabolites, and drug levels in hair peaked 4 weeks after dosing (Karatt et al., Rapid Commun Mass Spectrom 2023).
For other SARMs in the library, see ostarine, ligandrol and GSK2881078, another indole-class SARM.
Key takeaways
- One compound, three names. LY2452473 (Lilly), TT701 (Transition) and OPK-88004 (OPKO) are the same drug, as shown by the license agreement, OPKO’s patent disclosures and the trial registry.
- Lean mass up, function unchanged. In prostate cancer survivors, 5 mg/day added about 1.5 kg of lean mass in 12 weeks vs 0.3 kg on placebo, but strength, physical performance and sexual function did not improve.
- Sexual-function goals were not met. It did not improve erectile function in either the Lilly trial or the prostate cancer survivor trial.
- HDL and testosterone fall with dose. HDL dropped by about 13–18 mg/dL at 5–15 mg/day, and SHBG and total testosterone fell in a dose-related way.
- Long half-life, limited safety data. The parent drug’s half-life is about 27 hours, and all human data come from 12–16 week trials.
- Never approved, development stalled. The last trial was terminated in 2019. WADA bans it as a SARM.
Sources
- Yi P, Rehmel JF, Cassidy K, et al. Disposition and metabolism of LY2452473, a selective androgen receptor modulator, in humans. Drug Metab Dispos. 2012;40(12):2354–2364. PubMed.
- Pencina KM, Burnett AL, Storer TW, et al. A Selective Androgen Receptor Modulator (OPK-88004) in Prostate Cancer Survivors: A Randomized Trial. J Clin Endocrinol Metab. 2021;106(8):2171–2186. PubMed; PMC.
- Guo W, Pencina KM, Furtado JD, et al. Effect of Selective Androgen Receptor Modulator on Cholesterol Efflux Capacity, Size, and Subspecies of HDL Particles. J Endocr Soc. 2022;6(8):bvac099. PubMed.
- Dana-Farber Cancer Institute. A Selective Androgen Receptor Modulator for Symptom Management in Prostate Cancer (NCT02499497). Results posted 2021. ClinicalTrials.gov.
- OPKO Health. Effects and Safety of OPK-88004 Doses in Men With Signs and Symptoms of Benign Prostatic Hyperplasia (BPH) (NCT03297398). Results posted 2021. ClinicalTrials.gov.
- Eli Lilly and Company. A Study of LY900010 in Erectile Dysfunction (NCT01160289). ClinicalTrials.gov.
- Transition Therapeutics. Transition Therapeutics In-Licenses Phase 2 Drug Candidate from Lilly. Press release, May 6, 2015 (Form 6-K, Exhibit 99.1). SEC.
- Transition Therapeutics Ireland Limited and Eli Lilly and Company. License agreement (Form 6-K, Exhibit 99.1, filed May 11, 2015). SEC.
- OPKO Health. Annual report on Form 10-K for fiscal year 2016. SEC.
- OPKO Health. Annual report on Form 10-K for fiscal year 2025, filed February 26, 2026. SEC.
- Gavardinas K, Green JE, Jadhav PK, Matthews DP; Eli Lilly and Co. Tetrahydrocyclopenta[b]indole compounds as androgen receptor modulators. US Patent 7,968,587, granted June 28, 2011. Google Patents.
- National Center for Biotechnology Information. PubChem Compound Summary for CID 24963749 (LY2452473). PubChem.
- Noey EL, Yang Z, Li Y, et al. Origins of Regioselectivity in the Fischer Indole Synthesis of a Selective Androgen Receptor Modulator. J Org Chem. 2017;82(11):5904–5909. PubMed.
- Stacchini C, Botrè F, Comunità F, et al. Simultaneous detection of different chemical classes of selective androgen receptor modulators in urine by liquid chromatography-mass spectrometry-based techniques. J Pharm Biomed Anal. 2021;195:113849. PubMed.
- Karatt TK, Sathiq MA, Laya S, et al. Metabolic study of selective androgen receptor modulator LY2452473 in thoroughbred horses for doping control. Rapid Commun Mass Spectrom. 2023;37(9):e9491. PubMed.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA.
- Schedules of controlled substances: Schedule III. 21 CFR 1308.13. eCFR.