ACP-105: What the Research Shows About This Experimental SARM

Key takeaways

What Is ACP-105?

ACP-105 is a non-steroidal compound that acts on the androgen receptor and is classed in the scientific literature as a selective androgen receptor modulator, or SARM. Vendor and academic sources describe it as a nonsteroidal SARM with partial agonist activity relative to the natural androgen testosterone, meaning it activates the androgen receptor but produces a smaller maximal effect than testosterone itself in the assays where it has been tested.

Structurally, ACP-105 is described as an aniline-type SARM and is chemically related to two other experimental androgen receptor modulators, AC-262536 and vosilasarm (RAD140). Two CAS registry numbers appear across chemical vendor catalogs and the peer-reviewed literature for this compound, 899821-23-9 and 1048998-11-3; both are used to refer to ACP-105, with the compound carrying the IUPAC name 2-chloro-4-(3-hydroxy-3-methyl-8-azabicyclo[3.2.1]octan-8-yl)-3-methylbenzonitrile and the molecular formula C16H19ClN2O.

ACP-105 was discovered by scientists at ACADIA Pharmaceuticals as part of a broader effort to identify novel chemical classes of SARMs, ranging from full and partial agonists to full antagonists of the androgen receptor. The compound emerged from a high-throughput screen using receptor selection and amplification technology (R-SAT), and its discovery, structure-activity relationships, and initial pharmacological characterization were first reported in a 2008 conference abstract and a full 2009 paper in the Journal of Medicinal Chemistry.

How ACP-105 Was First Studied: Muscle, Bone, and Hormonal Effects

The original research program framed ACP-105 within the broader rationale for developing SARMs at all: clinical experience with testosterone suggested a wide range of potential indications for tissue-selective androgen receptor modulators, including hypogonadism, osteoporosis, CNS-related conditions, and muscle-wasting disorders, without the liabilities associated with testosterone itself.

In cell-based assays, ACP-105 was identified as a potent and selective androgen receptor agonist. In a two-week study in castrated male rats, the compound significantly improved anabolic parameters, including robust growth of the levator ani muscle, a standard rodent bioassay for androgenic anabolic activity, and it potently suppressed the luteinizing hormone surge that follows castration. Tissue selectivity was demonstrated by minimal trophic effects on the prostate in castrated animals and no detectable trophic effect on the prostate of intact rats, in contrast to the prostate stimulation typically seen with testosterone itself.

These findings place ACP-105's earliest and most extensively documented preclinical work squarely in the muscle and bone domain, consistent with the general SARM research rationale of the mid-2000s, rather than as a program conceived primarily around cognition.

Later Research: Cognition, Alzheimer's Models, and Radiation-Induced Impairment

Separately from the muscle and bone work, academic researchers subsequently investigated ACP-105 in rodent models relevant to the brain. In one study, ACP-105 was administered to female mice at 1 mg/kg per day and was found to inhibit radiation-induced decreases in contextual fear conditioning freezing time, a behavioral measure interpreted as reflecting a reversal of memory deficits; the same research also examined effects on MAP-2 immunoreactivity, a marker of neuronal structural integrity, in different brain regions of irradiated and sham-irradiated mice.

In a separate line of work, ACP-105 was tested in a gonadectomized triple-transgenic (3xTg) mouse model of Alzheimer's disease, a genetically engineered model that develops amyloid plaques and cognitive decline. Administered together with the selective estrogen receptor beta agonist AC-186 over several months, ACP-105 was associated with reduced brain levels of amyloid-beta (Aβ40 and Aβ42) and improvements in a marker of the enzymes that degrade amyloid-beta, alongside behavioral improvements in these mice; ACP-105 alone also reduced anxiety-like behavior in this model.

Most recently, an in silico pharmacokinetic characterization of ACP-105 modeled its absorption, distribution, metabolism, and excretion properties using multiple computational prediction methods, given that a comprehensive experimentally derived ADME profile does not yet exist for this compound. That analysis predicted high gastrointestinal absorption, moderate lipophilicity, strong plasma protein binding, and blood-brain barrier penetration in most models, with metabolism predicted to occur primarily through the CYP3A4 enzyme with lesser contributions from CYP2C9, CYP2C19, and CYP2D6. Separately, an in vitro measurement in human hepatocytes found a half-life of approximately 5.0 hours; this is a laboratory metabolic-stability measurement, not a human pharmacokinetic parameter derived from clinical dosing, since no such clinical studies have been conducted.

Human Clinical Trials and Regulatory Status

No component of the ACP-105 research program described above has progressed to registered human clinical trials. All published data on this compound comes from cell-based assays, rodent studies, in vitro human tissue preparations, and computational modeling. ACP-105 is not approved by the U.S. Food and Drug Administration or any other regulatory agency for any medical use, and no SARM of any kind currently holds FDA approval for human use; all SARMs remain investigational compounds that cannot legally be prescribed.

The FDA has repeatedly warned that body-building products containing SARMs, marketed illegally as dietary supplements, are unapproved drugs associated with serious safety concerns, including potential increases in the risk of heart attack, stroke, and life-threatening liver toxicity, and the agency has issued warning letters to companies distributing such products. Industry and public-health statements accompanying these actions have specifically listed ACP-105 among the named SARM ingredients of concern in illicit supplement products. Health authorities have also linked SARMs as a class to psychosis, sleep disturbances, sexual dysfunction, liver injury or failure, infertility, pregnancy miscarriage, and testicular shrinkage; because no dedicated human safety studies of ACP-105 itself exist, it is not possible to say which, if any, of these risks apply specifically to this compound at particular exposures, and the precautionary assumption is that risks broadly associated with the SARM class apply.

Status in Sport and Doping Control

Selective androgen receptor modulators as a class have been classified under the World Anti-Doping Agency's Prohibited List since 2008, listed within the S1.2 "Other Anabolic Agents" category, and are prohibited at all times, both in and out of competition, for athletes at every level. The current Prohibited List names several SARMs explicitly as examples, and also prohibits, under the same category, other substances with similar chemical structure or similar biological effects, a formulation intended to capture SARMs such as ACP-105 that are not individually named.

Consistent with this framework, ACP-105 has been described in the forensic and anti-doping chemistry literature as a novel non-steroidal SARM that is increasingly detected in anti-doping analyses, and dedicated analytical and metabolite-identification work has been published to support its detection in doping-control settings, reflecting its status as a substance of ongoing concern to anti-doping laboratories despite the absence of any approved medical use.

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