ACP-105

ACP-105 is a non-steroidal partial agonist at the androgen receptor (AR), developed by ACADIA Pharmaceuticals as part of the aniline-class SARM family that also includes AC-262536 and RAD-140. What makes it interesting for physique and looksmaxxing use is the combination of high AR binding affinity with lower intrinsic activity than a full agonist — you get meaningful anabolic signal in muscle and bone with much less activation in prostate and other accessory tissues.

High-Affinity Partial Agonism at the AR#

In vitro functional assays place ACP-105 at pEC₅₀ 9.0 against wild-type AR — essentially DHT-equivalent on a receptor-binding basis — but because it's a partial agonist, it fails to fully activate the receptor the way DHT or testosterone do. Practically, this means it occupies AR and drives transcription in a tissue-selective pattern: strong in muscle and CNS, muted in prostate. It's also why stacking ACP-105 on top of TRT is a real mechanism question, not a "more is more" story — at high enough concentrations it will compete with your endogenous testosterone for AR occupancy and behave like a soft antagonist in tissues where full agonism matters.

Tissue-Selective Anabolic Signalling#

The defining data point comes from the original ACADIA paper's castrate-rat (Hershberger) assay, which is the standard anabolic/androgenic selectivity screen:

"In the Hershberger assay, ACP-105 restored about 67% of the levator ani weight compared to DHT, while restoring only 21% of the prostate weight, displaying a myotropic-to-androgenic selectivity ratio of 3.2." — Schlienger N. et al., Journal of Medicinal Chemistry, 2009

That 3.2:1 muscle-to-prostate ratio is the mechanistic basis for why users report clean strength and density gains with minimal classic androgenic sides (acne, oily skin, aggressive shedding) at 10–15 mg/day. The selectivity arises from differential coactivator recruitment — ACP-105 stabilizes AR in a conformation that efficiently recruits the coregulators needed for muscle-specific gene transcription but fails to fully assemble the transcriptional machinery required in prostate tissue.

CNS Androgen Receptor Activity#

Unlike most SARMs, ACP-105 was originally positioned as a candidate for age-related cognitive decline — which is why there's unusually good CNS data for a compound in this class. It crosses into the brain and activates neuronal AR populations in the hippocampus and cortex.

"When administered to APP mice, ACP-105 significantly improved spatial memory performance and reduced soluble Aβ1-42 levels in the hippocampus." — George S. et al., ACS Chemical Neuroscience, 2013

A separate study showed preserved motor-coordination performance after cranial irradiation:

"ACP-105 preserved rotorod performance in irradiated mice, suggesting a protective effect on CNS function after cranial irradiation." — Dayger C. et al., Brain Research, 2011

For the physique user, this is the mechanism behind the "pre-workout feel" that dominates community logs — sharper focus, mood lift, and training aggression without the wired insomnia of RAD-140. It's also why sub-anabolic doses (5–10 mg/day) show up in nootropic/libido use-cases.

Partial HPTA Suppression#

Because ACP-105 binds AR potently in the hypothalamus and pituitary, it downregulates GnRH pulse frequency and blunts LH/FSH output — the standard SARM suppression mechanism. The partial-agonist character softens this relative to full agonists like LGD-4033, but it doesn't abolish it. Community bloodwork at 10–15 mg/day for 8 weeks consistently shows 30–60% suppression of total testosterone with partial LH/FSH blunting — enough to warrant a mini-PCT after longer or higher-dose runs, not enough to require a full nolvadex protocol for most users.

Non-Aromatizing, Non-5α-Reduced Profile#

ACP-105 is a small-molecule aniline, not a steroid. It cannot aromatize to estrogen and is not a substrate for 5α-reductase. This is mechanistically important for two reasons: (1) no water retention, no gyno risk, no on-cycle AI needed — and crucially, do not add an AI to an ACP-only cycle or you will crash E2; (2) the compound's effects on scalp and prostate are not amplified by DHT conversion, which is part of why the androgenic side-effect profile stays mild at standard doses.

Hepatic Metabolism and Clearance#

ACP-105 undergoes extensive Phase I hydroxylation followed by glucuronidation. Anti-doping metabolite mapping has characterized this pathway in detail:

"A dihydroxylated metabolite was identified as the preferred plasma biomarker, enabling reliable detection of ACP-105 misuse in anti-doping settings." — Broberg MN. et al., Metabolites, 2021

It is not a 17α-alkylated steroid and does not carry the hepatotoxic signature of orals like anadrol or superdrol — ALT/AST typically stay in range on standalone cycles. That said, it is still an oral xenobiotic being cleared through the liver, so stacking it with a second or third oral (S23, SR9009, LGD) meaningfully compounds hepatic load. Competitive athletes should note that the metabolite-based LC-MS/MS assays are already validated in both human and equine matrices — ACP-105 is detectable and WADA-prohibited at all times.

Common (most users)#

• HPTA suppression (partial) — Expect LH/FSH to drop and total T to fall roughly 30–60% on an 8-week run at 12.5–15 mg/day. Milder than LGD-4033 or RAD-140 at equivalent anabolic effect thanks to the partial-agonist profile, but real. Mitigation: keep cycles ≤10 weeks, run a mini-PCT (enclomiphene 12.5 mg/day × 4 weeks, or nolva 20/20/10/10) after any cycle of 8+ weeks at ≥12.5 mg/day, and pull bloods 2 weeks post-cycle to confirm restart.
• HDL drop / lipid shift — Standard SARM-class pattern, less severe than LGD at matched dose but still present. Mitigation: baseline lipid panel, re-check at week 4 and post-cycle; add 2–4 g/day fish oil and keep cardio in the week; if HDL craters below 30 mg/dL, cut dose or end the run early.
• Mild shedding / oily skin / minor acne — Uncommon at 10–15 mg, shows up more at 20+ mg. Mitigation: topical niacinamide or adapalene handle the skin side; ketoconazole shampoo for shedding. Anyone running a hair stack (fin/dut, topical AR antagonists) should stay the course.
• Irritability or disrupted sleep at higher doses — Subset of users report a CNS "wired" feel above 15 mg, especially if dosed PM. Mitigation: split AM/pre-workout; avoid evening dosing.
• Appetite uptick — Mild, helpful on a lean bulk, neutral-to-annoying on a cut. No mitigation needed — plan macros around it.

"ACP-105 restored about 67% of the levator ani weight compared to DHT, while restoring only 21% of the prostate weight, displaying a myotropic-to-androgenic selectivity ratio of 3.2." — Schlienger et al., Journal of Medicinal Chemistry (2009)

Uncommon (dose-dependent or individual)#

• Deeper suppression at 20+ mg — Above ~20 mg/day the partial-agonist advantage erodes and suppression starts looking like a full-agonist SARM. Back off to 15 mg or end the cycle if post-cycle total T fails to clear 300 ng/dL within 4 weeks of stopping.
• ALT/AST elevation when stacked — ACP-105 alone rarely moves LFTs, but stacking a second oral (S23, SR9009, or any 17-aa) raises liver load. Check LFTs mid-cycle if running ≥2 orals; if ALT crosses ~2× ULN, drop the second oral.
• Elevated blood pressure — Uncommon at sane doses but possible in anyone already running AAS on top. Monitor at home; if resting BP climbs over 140/90, address it with tadalafil 5 mg/day or telmisartan before pushing further.
• Flat/low libido post-cycle — Reflects the suppression, not a direct compound effect. Resolves on its own or with a mini-PCT. Persistent low libido 6+ weeks out warrants a full hormone panel.
• Shedding in hair-sensitive users — Less aggressive than DHT-based AAS but the partial AR activation can still push susceptible scalps. Pre-existing topical antiandrogen routine (RU58841, topical fin) handles it.

Rare but serious#

• Severe lipid dysregulation — HDL under 25 mg/dL or total cholesterol climbing past 260 mg/dL. Warning signs: none symptomatic — this is why you draw bloods. Stop the cycle and remediate with diet, cardio, and a statin if persistent.
• Cholestatic liver signal — Not documented in preclinical work but any oral xenobiotic can do this in a susceptible user. Warning signs: dark urine, pale stools, RUQ pain, jaundice, pruritus. Stop immediately and get an LFT panel plus GGT/bilirubin.
• Persistent post-cycle HPTA shutdown — Rare with ACP-105 specifically, but any user who fails to restart after 8 weeks off + a proper SERM PCT needs a full endocrine workup.
• Underdosed / misidentified product — ACP-105 is a low-volume research chem and vendor QC is inconsistent. The serious risk here isn't ACP-105 itself but whatever else is in the bottle. Buy only from vendors publishing batch-level HPLC COAs.

Hard contraindications#

• Active or prior hormone-sensitive cancer (prostate, testicular, any AR-driven malignancy) — AR agonism is off-limits, full stop.
• Untreated hyperlipidemia or familial hypercholesterolemia — SARMs will worsen it. Get lipids in range first.
• Pregnancy or near-term conception plans (either partner) — suppresses spermatogenesis and has zero human teratogenicity data. Do not run it.
• Adolescents / anyone still growing — androgens accelerate epiphyseal closure.
• Competitive / tested athletes — WADA-prohibited at all times under S1.2, and modern assays specifically target ACP-105 metabolites.

"A dihydroxylated metabolite was identified as the preferred plasma biomarker, enabling reliable detection of ACP-105 misuse in anti-doping settings." — Broberg et al., Metabolites (2021)

"The main metabolites observed in urine were monohydroxylated glucuronides, providing robust targets for anti-doping assays." — Subhahar et al., Drug Testing and Analysis (2021)

Gender-specific and PCT considerations#

Men: Mini-PCT after cycles of 8+ weeks at ≥12.5 mg/day — enclomiphene 12.5 mg/day × 4 weeks, or nolvadex 20/20/10/10. Confirm restart with a 2-week-post-cycle hormone panel (total T, free T, LH, FSH, E2). Restart is generally smooth relative to LGD or RAD.

Women: Not a well-explored compound in female physique circles. The partial-agonist profile is theoretically better tolerated than RAD-140, but virilization risk (voice deepening, clitoral enlargement, hair pattern change) is still present and the first two are irreversible. If used, cap at 5 mg/day and 6 weeks maximum, and stop at the first sign of voice change.

Do not run an aromatase inhibitor on an ACP-only cycle — ACP-105 doesn't aromatize, so an AI will crash E2 into joint pain, libido loss, and lipid damage with no upside. No on-cycle AI is needed. If you're running ACP layered on exogenous test, the AI decision is driven by the test, not by ACP.