Overview
ACE-031, also known by the CAS number 1621169-52-5, is a synthetic peptide that functions as a myostatin inhibitor, placing it within the broader category of muscle-regulating research compounds. It is designed to mimic and block the activity of the activin type IIB receptor (ActRIIB), a pathway that plays a role in regulating skeletal muscle mass in mammals. The peptide is derived from a segment of the human activin receptor and has been studied in preclinical research settings, including non-human primate models, to better understand how myostatin and related signaling proteins influence muscle tissue. Because of its potential to affect muscle physiology, it has also attracted attention in the context of anti-doping research, and is listed among prohibited substances by the World Anti-Doping Agency. ACE-031 is intended strictly for laboratory and scientific research purposes and is not approved for human use or consumption.
Research & Bioactivity
ACE-031, also known as Ramatercept, is a soluble fusion protein constructed from a fragment of the human activin receptor type IIB (ActRIIB) linked to an immunoglobulin Fc region, and researchers have studied it primarily in the context of skeletal muscle biology. Studies have examined its ability to act as a ligand trap, binding and blocking signaling molecules such as myostatin and activin A, which are known to negatively regulate muscle growth. Research conducted in murine models has investigated associations between ActRIIB pathway blockade and changes in skeletal muscle mass and functional performance, and these findings prompted further study in non-human primate models, including the common marmoset. In non-human primate studies, researchers have examined whether pharmacological inhibition of ActRIIB ligands produces measurable increases in muscle mass and strength, with findings intended to inform understanding of pathways relevant to conditions involving muscle wasting. Because of its potential to influence muscle tissue biology, ACE-031 has also attracted attention in the context of sports science research and anti-doping efforts, and it currently appears on the World Anti-Doping Agency list of prohibited substances. All published research involving ACE-031 has been conducted in preclinical or controlled laboratory settings, and it is not approved for human use.
Published Research
ACE-031, a soluble activin type IIB receptor, increases muscle mass and strength in the common marmoset (Callithrix jacchus).
Cadena SM, Bogdanovich S, Khurana TS, Pullen A, Pearsall RS, et al. — 2026
Pharmacological blockade of ligands for the activin receptor type IIB (ActRIIB) e.g., myostatin and activin A is associated with improvements in murine skeletal muscle mass and function. The efficacy of a similar treatment approach in a non-human primate (NHP) model would suggest a greater likelihood of success in the treatment of humans suffering from chronic myopathies. In the present study, we elucidate the potential therapeutic benefit of ACE-031, a therapeutic protein consisting of the ActRIIB extracellular region fused to human IgG1, in the common marmoset (Callithrix jacchus). Marmosets were randomized to receive ACE-031 or vehicle control (10 mM Tris buffered saline; TBS) for 14 weeks. Body composition was measured weekly throughout the experimental period and morphometric analysis and contractile properties of skeletal muscle were assessed terminally. There was a significant main effect of time and time x treatment interaction for lean body mass, such that marmosets administered ACE-031 were greater at euthanasia compared to baseline; this was not observed in the vehicle-treated controls. Biceps brachii exhibited a significant increase in the cross-sectional area of both type I and type II fibers and ex vivo contractile properties of the EDL showed an increase in absolute and specific force production. The efficacy of ACE-031 in non-human primates provides optimism that a therapeutic strategy that targets multiple negative regulators of skeletal muscle may be beneficial in treating myopathies in humans.
ACE-031, a Soluble Activin Type IIB Receptor, Increases Muscle Mass and Strength in the Common Marmoset (Callithrix jacchus).
Cadena SM, Bogdanovich S, Khurana TS, Pullen A, Pearsall RS, et al. — 2025
AIM: Pharmacological blockade of ligands for the activin receptor type IIB (ActRIIB) e.g., myostatin and activin A is associated with improvements in murine skeletal muscle mass and function. The efficacy of a similar treatment approach in a non-human primate (NHP) model would suggest a greater likelihood of success in the treatment of humans suffering from chronic myopathies. In the present study, we elucidate the potential therapeutic benefit of ACE-031, a therapeutic protein consisting of the ActRIIB extracellular region fused to human IgG1, in the common marmoset (Callithrix jacchus). METHODS: Marmosets were randomized to receive ACE-031 or vehicle control (10 mM Tris buffered saline; TBS) for 14 weeks. Body composition was measured weekly throughout the experimental period and morphometric analysis and contractile properties of skeletal muscle were assessed terminally. RESULTS: Marmosets administered ACE-031 showed a significant increase in body weight and lean body mass from baseline, while no change was seen in the vehicle-treated controls. Biceps brachii exhibited a significant increase in the cross-sectional area of both type I and type II fibers and ex vivo contractile properties of the EDL showed an increase in absolute and specific force production. CONCLUSION: The efficacy of ACE-031 in non-human primates provides optimism that a therapeutic strategy that targets multiple negative regulators of skeletal muscle may be beneficial in treating myopathies in humans.
Gel Electrophoretic Detection of Black Market ACE-031.
Reichel C, Filip T, Gmeiner G, Thevis M — 2025
The usage of ACE-031 (Ramatercept), a dimeric fusion protein consisting of a human activin receptor IIB (ACVR2B) fragment linked to an Fc-part of human IgG1, is banned according to chapter S4.3 of the "WADA 2024 List of Prohibited Substances and Methods" due to its potential performance enhancing properties. While ACE-031 has not yet been pharmaceutically approved, it is sold as research chemical on the "black market" (BM). The article presents a study on BM ACE-031 products and its detection by gel-electrophoresis and Western blotting. Of 14 tested products, only 12 contained an ACVR2B-immunoreactive protein. Electrophoretic separation by SDS-PAGE also showed that the 12 ACVR2B-products contained many other proteins in addition to the main compound (ca. 58.4 kDa). Further analyses by mass spectrometry and immunoblotting revealed that the 12 products contained the full-length human activin receptor IIB instead of ACE-031. The absence of an Fc-fusion protein was further confirmed by treatment with IdeS protease, which was unable to cleave the BM products. In addition, it was demonstrated that the protocol we developed to detect luspatercept (another ACVR2B-Fc fusion protein) in human serum could also be successfully applied for the detection of BM ACE-031. Because administering black market products to human subjects was not ethically justifiable, a study was conducted with rats. In rat serum, BM ACE-031 was detectable up to 48 h post administration. However, due to the relatively high dose applied (10 mg/kg body weight) and possible differences in metabolism, the detection window may be different in humans.
The relationship between myodural bridge, atrophy and hyperplasia of the suboccipital musculature, and cerebrospinal fluid dynamics.
Yang H, Wei XS, Gong J, Du XM, Feng HB, et al. — 2023
The Myodural Bridge (MDB) is a physiological structure that is highly conserved in mammals and many of other tetrapods. It connects the suboccipital muscles to the cervical spinal dura mater (SDM) and transmits the tensile forces generated by the suboccipital muscles to the SDM. Consequently, the MDB has broader physiological potentials than just fixing the SDM. It has been proposed that MDB significantly contributes to the dynamics of cerebrospinal fluid (CSF) movements. Animal models of suboccipital muscle atrophy and hyperplasia were established utilizing local injection of BTX-A and ACE-031. In contrast, animal models with surgical severance of suboccipital muscles, and without any surgical operation were set as two types of negative control groups. CSF secretion and reabsorption rates were then measured for subsequent analysis. Our findings demonstrated a significant increase in CSF secretion rate in rats with the hyperplasia model, while there was a significant decrease in rats with the atrophy and severance groups. We observed an increase in CSF reabsorption rate in both the atrophy and hyperplasia groups, but no significant change was observed in the severance group. Additionally, our immunohistochemistry results revealed no significant change in the protein level of six selected choroid plexus-CSF-related proteins among all these groups. Therefore, it was indicated that alteration of MDB-transmitted tensile force resulted in changes of CSF secretion and reabsorption rates, suggesting the potential role that MDB may play during CSF circulation. This provides a unique research insight into CSF dynamics.
The relationship between myodural bridges, hyperplasia of the suboccipital musculature, and intracranial pressure.
Li C, Yue C, Liu ZC, Gong J, Wei XS, et al. — 2022
During mammalian evolution, the Myodural Bridges (MDB) have been shown to be highly conserved anatomical structures. However, the putative physiological function of these structures remains unclear. The MDB functionally connects the suboccipital musculature to the cervical spinal dura mater, while passing through the posterior atlanto-occipital and atlanto-axial interspaces. MDB transmits the tensile forces generated by the suboccipital muscles to the cervical dura mater. Moreover, head movements have been shown to be an important contributor to human CSF circulation. In the present study, a 16-week administration of a Myostatin-specific inhibitor, ACE-031, was injected into the suboccipital musculature of rats to establish an experimental animal model of hyperplasia of the suboccipital musculature. Using an optic fiber pressure measurement instrument, the present authors observed a significant increase in intracranial pressure (ICP) while utilizing the hyperplasia model. In contrast, surgically severing the MDB connections resulted in a significant decrease in intracranial pressure. Thus, these results indicated that muscular activation of the MDB may affect CSF circulation, suggesting a potential functional role of the MDB, and providing a new research perspective on CSF dynamics.