ACE-031 Research Guide — ActRIIB Decoy Fusion Protein, Broad TGF-β Ligand Trap Mechanism & Clinical Data (2026)
- ACE-031 (also designated ACVR2B-Fc; ActRIIB-IgG1) is a recombinant fusion protein consisting of the extracellular domain of human activin receptor type IIB (ActRIIB; ACVR2B) fused to the Fc portion of human IgG1. It was developed by Acceleron Pharma (in collaboration with Shire compound) as a therapeutic candidate for Duchenne muscular dystrophy (DMD) and other muscle-wasting conditions. Unlike conventional peptides, ACE-031 is a large biological construct that functions as a soluble decoy receptor — a “ligand trap” that circulates freely and sequesters myostatin and multiple related TGF-β superfamily ligands before they can bind and signal through membrane-bound ActRIIA/B on muscle cells. YPB offers research-grade ACE-031 as YPB.249 (Research Use Only).
- Mechanism: Under normal physiology, myostatin (GDF-8) and related ligands (activin A, activin B, GDF-11, BMP-2, BMP-7) bind ActRIIA/B on muscle satellite cells and mature fibers, signaling through Smad2/3 phosphorylation to suppress muscle protein synthesis, inhibit satellite cell differentiation, and limit muscle mass (the endogenous “muscle brake” system). ACE-031’s soluble ActRIIB extracellular domain binds these same ligands in circulation with high affinity, preventing them from reaching membrane-bound receptors and thereby releasing the myostatin/activin suppression on muscle growth. The IgG1-Fc fusion extends half-life to 10–15 days (confirmed in human Phase 1 PK data) by enabling FcRn-mediated albumin recycling.
- Human clinical evidence: Phase 1 (Attie et al. 2013, PMID: 23169607) in 48 healthy postmenopausal women: well tolerated at most doses; significant dose-dependent increase in thigh muscle volume (5–9%); lean body mass increase; fat mass reduction; bone mineral density effects. Phase 2 DMD (2017, PMID: 27462804): terminated early due to epistaxis and telangiectasias at higher doses. Clinical development permanently discontinued 2013.
- Critical safety and regulatory context: (1) Clinical development discontinued by Acceleron Pharma and Shire compound in 2013 following vascular adverse events (epistaxis, telangiectasias attributed to off-target BMP9 and related vascular ligand sequestration). (2) WADA prohibited under S4.3 (myostatin inhibitors). (3) A 2025 anti-doping study found that 14 black-market products marketed as ACE-031 contained full-length ActRIIB rather than the Fc fusion protein; most did not match the authentic compound. Research-grade COA verification is critical. YPB.249. Research Use Only (RUO). Updated April 2026.
What Is ACE-031 and What Makes It Unique Among Muscle Biology Research Tools?
10–15 Day Half-Life (Human PK)
5–9% Muscle Volume Increase in Phase 1
ACE-031 occupies a unique position in the muscle biology research toolbox: it is not a selective myostatin inhibitor — it is a pan-TGF-β superfamily ActRIIB ligand trap that removes the entire spectrum of negative muscle regulators that signal through the ActRIIB receptor pathway simultaneously. Updated April 2026. This breadth is both its primary research advantage (maximum myostatin-pathway inhibition; removal of all ActRIIB-dependent muscle suppression) and its primary safety limitation (concurrent removal of vascular and other tissue ligands that signal through the same receptor system).
ACE-031 was developed by Acceleron Pharma based on foundational work by Lee et al. (2005) demonstrating that a soluble ActRIIB receptor produced up to 60% muscle mass increase in mice within two weeks — an effect substantially larger than myostatin-specific antibodies achieved, which confirmed that additional ActRIIB ligands beyond myostatin (activin A, activin B, GDF-11) also function as negative regulators of muscle mass in vivo. This research established that broadly blocking ActRIIB signaling was more potent than blocking myostatin alone, and ACE-031 was designed to replicate this pan-ActRIIB blockade in a human-compatible fusion protein format.
Key Characteristics
| Parameter | Value |
|---|---|
| Full Designation | ACE-031; ACVR2B-Fc; ActRIIB-IgG1; soluble activin receptor type IIB |
| Classification | Recombinant fusion protein (NOT a peptide; large biological construct); extracellular domain of human ActRIIB fused to Fc portion of human IgG1 |
| YPB SKU | YPB.249 |
| Developer | Acceleron Pharma (with Shire compound); clinical development permanently discontinued 2013 |
| Mechanism | Soluble decoy receptor / ligand trap: circulates freely and sequesters myostatin (GDF-8), activin A, activin B, GDF-11, BMP-2, BMP-7, and other TGF-β superfamily ligands before they reach membrane-bound ActRIIA/B on target cells |
| Primary Ligands Trapped | Myostatin (GDF-8) — primary muscle mass negative regulator; activin A — additional muscle and other tissue regulator; GDF-11 — muscle/aging; BMP-9 — vascular; BMP-2/7 — bone; activin B |
| Smad Pathway | By trapping ligands, ACE-031 prevents ligand binding to membrane-bound ActRIIB/ALK4/5 → prevents Smad2/3 phosphorylation → removes suppression of muscle protein synthesis, satellite cell differentiation, and fiber growth |
| Half-Life | 10–15 days (confirmed in Phase 1 human PK; Attie et al. 2013; T½ extended by IgG1-Fc FcRn-mediated recycling) |
| Clinical Evidence | Phase 1 (healthy women, 2013): 5–9% thigh muscle volume increase, lean mass up, fat mass down; Phase 2 DMD (2017): terminated early due to epistaxis/telangiectasias |
| Clinical Status | All human clinical development permanently discontinued (2013). No active trials. Not research-grade (received orphan compound designation 2010; withdrawn from development). |
| FDA Status | Not research-grade. Orphan compound designation for DMD granted 2010; clinical development discontinued 2013. Research Use Only (RUO). |
| WADA Status | Prohibited — S4.3 Myostatin Inhibitors (includes “myostatin-binding proteins”; all times, in- and out-of-competition), WADA 2025 |
| Storage | Lyophilized: −20°C. As a recombinant fusion protein: reconstitute gently (do not vortex); use low-protein-binding containers; hold 2–8°C up to 14 days after reconstitution; avoid freeze-thaw cycles |
How Does ACE-031 Work? The Myostatin/Activin Pathway and Ligand Trap Mechanism
The Myostatin “Muscle Brake” System
Myostatin (GDF-8; growth differentiation factor 8) is a member of the TGF-β superfamily secreted predominantly by skeletal muscle itself. It is the primary endogenous negative regulator of muscle mass: animals with natural myostatin loss-of-function mutations (Belgian Blue cattle; whippet dogs; a documented human child with myostatin loss-of-function) display dramatic muscular hypertrophy. Myostatin binds ActRIIB on the surface of muscle satellite cells and mature muscle fibers, activating the ALK4/5 co-receptor → phosphorylating Smad2 and Smad3 → Smad2/3 complex enters nucleus → activates genes that inhibit muscle protein synthesis (reduce mTOR activity) and suppress satellite cell differentiation (block MyoD expression). The net effect is a constitutive molecular “brake” on muscle mass accumulation that keeps muscle within physiological bounds.
Beyond Myostatin: Why ActRIIB Blockade Outperforms Myostatin-Specific Inhibition
The critical insight from Lee et al. (2005) was that when a soluble ActRIIB extracellular domain was used to mice, muscle mass increased by up to 60% — far more than achieved by myostatin-specific antibodies or genetic myostatin deletion alone. The explanation: ActRIIB is also the signaling receptor for activin A, activin B, GDF-11, and several other TGF-β family members that also serve as negative regulators of muscle mass. By blocking the entire ActRIIB pathway rather than just myostatin, these additional suppressors are simultaneously neutralized. ACE-031 replicates this pan-ActRIIB blockade: its soluble ActRIIB extracellular domain binds all ligands that normally signal through ActRIIB, providing broader suppression of the muscle-limiting signaling network.
What Research Applications Has ACE-031 Been Studied For?
Muscle Wasting Disease Research (DMD, Sarcopenia, Cachexia)
ACE-031’s primary research application is studying the ActRIIB/myostatin/activin pathway in muscle wasting models. Published preclinical data demonstrated ACE-031 increased muscle mass and strength across multiple mouse models: mdx (DMD model); ALS; corticosteroid-induced muscle loss; androgen deprivation; age-related sarcopenia. These preclinical results supported the clinical development program. For researchers studying the molecular mechanisms of muscle wasting, ACE-031 is the reference ActRIIB pan-inhibition tool for establishing the maximum achievable effect of blocking all negative ActRIIB-dependent muscle suppression simultaneously.
Body Composition Research
Phase 1 clinical data (Attie et al. 2013) documented simultaneous increase in lean body mass and decrease in fat mass at multiple doses — indicating that ActRIIB pathway inhibition affects both muscle and adipose tissue biology. The fat reduction effect may reflect activin A and/or GDF-11 signaling roles in adipose tissue metabolism. These dual body composition effects make ACE-031 a useful tool for studying the intersection of muscle and fat mass regulation through the TGF-β superfamily axis.
Bone Biology Research
ActRIIB mediates signaling for BMP-2, BMP-7, and activins in bone tissue. ACE-031 has been shown to increase bone mineral density in preclinical models, potentially through activin signaling inhibition in osteoclasts or direct BMP signaling effects on osteoblasts. For DMD research subjects (who experience progressive bone loss from the disease and corticosteroid treatment), this bone effect was viewed as potentially therapeutic. It is also a confounding variable in ACE-031 muscle research that should be controlled for in skeletal biology studies.
What Does the Clinical Data Show?
| Trial | Design / Population | Key Finding & Adverse Events | Year |
|---|---|---|---|
| Phase 1 SAD Study — Attie et al. | Double-blind, placebo-controlled, single ascending dose (SAD) / 48 healthy postmenopausal women / doses 0.02–3 mg/kg SC | Well tolerated overall; dose-dependent mean T½ 10–15 days; significant increase in thigh muscle volume (5–9% at higher doses); lean body mass increase; fat mass decrease; bone density effects. AUC and Cmax increased linearly with dose. Adverse events: injection site erythema at higher doses; no serious or severe events. (Muscle Nerve, 2013, PMID: 23169607) | 2013 |
| Phase 2 DMD Trial | Randomized, double-blind, placebo-controlled, ascending dose / ambulatory boys with DMD / SC every 2–4 weeks | ACE-031 not associated with serious adverse events at lower doses. Study stopped after second dosing regimen due to potential safety concerns: epistaxis (nosebleeds) and telangiectasias (small abnormal blood vessel formation). Attributed to off-target sequestration of vascular BMP-9/BMP-10 ligands. Clinical development permanently discontinued following this finding. (Muscle Nerve, 2017, PMID: 27462804) | 2017 |
| Preclinical (mouse models) | Multiple models: mdx (DMD), ALS, corticosteroid-atrophy, age-related sarcopenia | ACE-031/soluble ActRIIB increased muscle mass, strength, and physical function across all models. Lee et al. 2005 foundational data: up to 60% muscle mass increase in wild-type mice with soluble ActRIIB (effect attenuated but not eliminated in myostatin KO mice, confirming additional ActRIIB ligands contribute). Preclinical results strongly supported clinical translation; vascular adverse events were not predicted by rodent models. | 2005–2010 |
| 2025 Anti-doping product analysis | 14 black-market products marketed as ACE-031 | Only 12 contained ACVR2B-immunoreactive protein. None matched the authentic ACE-031 fusion protein profile; most contained full-length ActRIIB rather than the extracellular domain Fc fusion. Multiple additional contaminating proteins detected. Underscores importance of research-grade COA verification for authentic compound identity. | 2025 |
How Does ACE-031 Compare to Other Muscle and Anabolic Research Compounds?
| Parameter | ACE-031 (ACVR2B-Fc) | GDF-8 (Myostatin; YPB.233) | BPC-157 | TB-500 |
|---|---|---|---|---|
| Mechanism | Pan-ActRIIB ligand trap: removes myostatin + activin A/B + GDF-11 + BMP-2/7/9 from circulation; prevents Smad2/3 signaling in muscle | The endogenous ligand itself; used to study myostatin’s direct inhibitory effects on satellite cells / Smad2/3 signaling / muscle atrophy induction in research models | Tissue repair; BPC-157-responsive growth factor upregulation; angiogenesis; VEGF, EGF pathways | Actin-sequestering; thymosin β4 analog; cell migration, wound healing, anti-inflammatory |
| Classification | Recombinant fusion protein (large biological; not a traditional peptide) | Endogenous TGF-β superfamily signaling protein; research antagonist tool vs. ACE-031 | 15-AA synthetic peptide; BPC-157 | 43-AA thymosin β4 analog |
| Research Relationship | Inhibits myostatin/activin signaling; used as inhibitor/blocker for ActRIIB pathway research | Activates myostatin/ActRIIB signaling; used as agonist to induce atrophy / study inhibitory mechanisms (paired with ACE-031 for full inhibitor/agonist research toolkit) | Orthogonal tissue repair mechanism; complementary to muscle mass biology | Orthogonal repair/regeneration; complementary to structural muscle research |
| Human Clinical Data | Phase 1 (2013): 5–9% muscle volume increase; Phase 2 (2017): terminated (epistaxis/telangiectasias). All clinical development discontinued. | Endogenous protein; human physiology well-characterized; research-grade used in atrophy induction models | Phase 2 gastric ulcer data; preclinical data across multiple models; no large-scale RCT | Phase 2 cardiac data (thymosin β4 related); preclinical repair models |
| WADA Status | Prohibited S4.3 (myostatin inhibitors) | Not listed (endogenous; used in research only) | Not listed 2025 | Not listed 2025 |
| YPB SKU | YPB.249 — see product | YPB.233 — see guide | YPB.201 — see guide | YPB.204 — see guide |
ACE-031 and GDF-8 (myostatin) form the most direct pharmacological pair in the muscle biology catalog: ACE-031 blocks the ActRIIB pathway; GDF-8 activates it. Using both together in the same research program provides the full inhibitor-agonist toolkit for characterizing ActRIIB/myostatin signaling in muscle models (see the GDF-8 Research Guide). For tissue repair and regeneration research, BPC-157 (see the BPC-157 Research Guide) and TB-500 provide orthogonal repair mechanisms that can be studied alongside or independently of the myostatin mass regulation axis.
What Should Researchers Know About ACE-031 Handling and Verification?
Fusion Protein Handling Requirements
ACE-031 is a large recombinant fusion protein, not a conventional small peptide. Handling best practices for fusion proteins apply: (1) reconstitute gently by adding buffer along the vial wall rather than directly onto the lyophilized cake; do not vortex; invert gently to dissolve; (2) use low-protein-binding microcentrifuge tubes and pipette tips at dilute concentrations to minimize surface adsorption; (3) avoid freeze-thaw cycles after reconstitution; prepare single-use aliquots from lyophilized stock; (4) filter through 0.22 µm syringe filter before use in sterile in vitro applications.
COA Verification: Critical for Authenticity
A 2025 anti-doping study examined 14 black-market ACE-031 products and found that none matched the authentic ACVR2B extracellular domain-IgG1-Fc fusion protein structure; most contained full-length ActRIIB instead. This finding means that compound identity verification beyond simple HPLC is essential for ACE-031 research. Key COA requirements: SDS-PAGE (should show the characteristic Fc-fusion protein molecular weight band under reducing/non-reducing conditions); Western blot with anti-ACVR2B antibody (confirms ActRIIB extracellular domain identity); functional activity assay (bioassay confirming myostatin/activin binding/neutralization at expected EC50). HPLC and MS alone are insufficient for fusion protein identity confirmation. All YPB ACE-031 batches include lot-traceable COA documentation through the COA Library.
Storage
Lyophilized: −20°C for up to 24 months. Reconstituted: 2–8°C, up to 14 days in single-use aliquots. As with all IgG-Fc fusion proteins, avoid pH extremes and repeated mechanical stress.
Key Research Findings
- Pan-ActRIIB ligand trap (not just myostatin): Sequesters GDF-8 (myostatin) + activin A + activin B + GDF-11 + BMP-2/7 + BMP-9; pan-ActRIIB blockade is more potent than myostatin-specific antibodies (up to 60% muscle mass increase in mice vs. lower gains with myostatin-only blockade; Lee et al. 2005).
- Phase 1 (Attie 2013, PMID: 23169607): 5–9% thigh muscle volume increase; lean mass up; fat mass down; T½ 10–15 days; generally well tolerated at most doses. The only human data showing clinically meaningful acute muscle volume increase for any ActRIIB inhibitor class compound.
- Phase 2 DMD terminated (PMID: 27462804): Epistaxis and telangiectasias at higher doses; attributed to off-target BMP-9/BMP-10 vascular ligand sequestration. Clinical development permanently discontinued 2013. This is the most important safety context for any ACE-031 research protocol.
- BMP-9 vascular liability: The same breadth that produces superior muscle effects also disrupts vascular BMP-9 signaling; subsequent ActRIIB inhibitor development (KER-065) specifically reduced BMP-9 affinity 400-fold to avoid this liability.
- 10–15 day half-life: IgG1-Fc extends half-life dramatically vs. any small peptide; allows infrequent dosing in mouse and primate research models.
- Black-market adulteration widespread (2025): 14/14 tested black-market ACE-031 products were inauthentic; SDS-PAGE, Western blot, and functional bioassay are required for authentic compound verification.
- WADA S4.3 Prohibited (myostatin inhibitors): Recognized potent muscle mass-increasing activity confirmed by human clinical data.
- Fusion protein, not a peptide: Requires gentle reconstitution, low-protein-binding containers, no vortexing; different handling from conventional synthetic peptides.
Browse the Full Research Catalog
Market Demand and Research Interest
| Demand Indicator | ACE-031 Data Point |
|---|---|
| Research context | ActRIIB/myostatin pathway; DMD biology; muscle wasting; sarcopenia; body composition; TGF-β superfamily signaling |
| Human clinical context | Phase 1 (2013): most striking acute muscle volume increase data of any ActRIIB inhibitor class; Phase 2 terminated (2017); development discontinued; research interest in understanding vascular adverse event mechanism |
| Unique catalog position | Only pan-ActRIIB ligand trap in YPB catalog; only recombinant fusion protein; combined with GDF-8, provides the complete myostatin pathway agonist/antagonist toolkit |
| Research legacy | Foundational compound in ActRIIB inhibitor field; informed all subsequent myostatin/activin pathway compound development (KER-065, apitegromab, trevogrumab, luspatercept) |
| WADA S4.3 | Prohibited; drives research interest from anti-doping community in addition to muscle biology researchers |
| Keyword difficulty range | Low (KD <10) |
How Can Researchers Offer ACE-031 Under Their Own Brand?
Wholesale Pricing & Margin Analysis
| SKU | Compound | Premier ($497/mo) | Core ($297/mo) | Suggested MSRP | Premier Margin |
|---|---|---|---|---|---|
| YPB.249 (RUO) | ACE-031 (ActRIIB-IgG1 Fc fusion protein) | TBC Premier | TBC Core | TBC | TBC at Premier tier |
Contact the YPB team for confirmed Premier and Core tier pricing. Use the YPB Profit Calculator to model projected revenue. White-label brands offering ACE-031 alongside GDF-8 create the complete ActRIIB pathway agonist/antagonist research toolkit — the only combination that enables both directional studies (inducing muscle atrophy via GDF-8 and blocking it via ACE-031) from a single buyer audience. Download the full catalog for all muscle biology category pricing.
Methodology & Data Sources
Methodology & Data Sources
Scientific literature: PubMed searched for “ACE-031,” “ACVR2B-Fc,” “soluble activin receptor IIB,” and “myostatin activin inhibitor muscle.” Search conducted through April 2026.
Key sources: Attie et al. (2013) Muscle Nerve (PMID: 23169607; Phase 1 SAD study); Campbell et al. (2017) Muscle Nerve (PMID: 27462804; Phase 2 DMD termination); Lee et al. (2005) PLoS One (foundational soluble ActRIIB mouse data); bioRxiv 2025 (marmoset ACE-031 data with KER-065 context); PeptideInsight ACE-031 profile (2025 anti-doping adulteration study); Cenexa Research Library.
Limitations: All human clinical development has been permanently discontinued (2013) due to vascular adverse events; ACE-031 is no longer in active compound development. The epistaxis and telangiectasias from Phase 2 DMD reflect an intrinsic liability of pan-ActRIIB ligand trapping (BMP-9/10 vascular sequestration) that is important to communicate in any research context. Research-grade product identity verification is critical given widespread black-market adulteration documented in 2025. This article is for educational purposes only.
References
- Attie, K. M., Borgstein, N. G., Yang, Y., Condon, C. H., Wilson, D. M., Pearsall, A. E., Kumar, R., Willins, D. A., Seehra, J. S., & Sherman, M. L. (2013). A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve, 47(3), 416–423. PMID: 23169607
- Campbell, C., McMillan, H. J., Mah, J. K., Tarnopolsky, M., Selby, K., McClure, T., Wilson, D. M., Sherman, M. L., Escolar, D., & Attie, K. M. (2017). Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: results of a randomized, placebo-controlled clinical trial. Muscle Nerve, 55(4), 458–464. PMID: 27462804
- Lee, S. J., Reed, L. A., Davies, M. V., Girgenrath, S., Goad, M. E., Tomkinson, K. N., Wright, J. F., Barker, C., Ehrmantraut, G., Holmstrom, J., Trowell, B., Gerber, B., Jiang, M. S., Sebald, S. M., Matzuk, M., Li, E., Liang, L. F., Quattlebaum, E., Stotish, R. L., & Wolfman, N. M. (2005). Regulation of muscle mass by follistatin and activins. Mol Endocrinol, 19(10), 2445–2462.
- McPherron, A. C., Lawler, A. M., & Lee, S. J. (1997). Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature, 387(6628), 83–90. (Myostatin/GDF-8 original characterization.)
- Sartori, R., Milan, G., Patron, M., et al. (2009). Smad2 and 3 transcription factors control muscle mass in adulthood. Am J Physiol Cell Physiol, 296(6), C1248–C1257. (Smad2/3 muscle biology context.)
- Suragani, R. N., Cawley, S. M., Li, R., et al. (2014). Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine β-thalassemia. Blood, 123(25), 3864–3872. (ActRIIB ligand trap field context; luspatercept precursor.)
- bioRxiv (2025). ACE-031, a soluble activin type IIB receptor, increases muscle mass and strength in the common marmoset. (Most recent preclinical data; Acceleron Pharma authors; KER-065 comparison context.)
- PeptideInsight (2025). Anti-doping product analysis: 14 black-market ACE-031 products characterized. (Adulteration/authenticity context.)
- Haidet, A. M., Rizo, L., Handy, C., et al. (2008). Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors. Proc Natl Acad Sci USA, 105(11), 4318–4322.
Frequently Asked Questions
ACE-031 (ACVR2B-Fc; ActRIIB-IgG1; YPB.249) is a recombinant fusion protein — the extracellular domain of human ActRIIB fused to IgG1-Fc. It is not a conventional peptide; it is a large biological construct functioning as a soluble decoy receptor (ligand trap). In research models, ACE-031 sequesters myostatin (GDF-8) and multiple related TGF-β superfamily ligands (activin A, activin B, GDF-11, BMP-2, BMP-7, BMP-9) in circulation, preventing them from binding membrane-bound ActRIIA/B on muscle cells, thereby blocking Smad2/3 signaling and releasing the myostatin/activin suppression on muscle mass. Human Phase 1 data (Attie 2013, PMID: 23169607): T½ 10–15 days; 5–9% thigh muscle volume increase; lean mass up, fat mass down. Phase 2 DMD terminated (PMID: 27462804) due to epistaxis/telangiectasias from BMP-9 vascular sequestration. All clinical development permanently discontinued 2013. WADA S4.3 Prohibited. Research Use Only (RUO). Updated April 2026.
ACE-031 is a pan-ActRIIB ligand trap, meaning it sequesters all TGF-β superfamily ligands that bind ActRIIB, not just myostatin. The foundational insight from Lee et al. (2005) was that used soluble ActRIIB to myostatin knockout mice still produced significant additional muscle mass increase — demonstrating that other ligands besides myostatin signal through ActRIIB and also function as negative regulators of muscle mass. Activin A, activin B, and GDF-11 were subsequently identified as the additional ActRIIB ligands that suppress muscle mass. A myostatin-specific antibody blocks only GDF-8; ACE-031 blocks GDF-8 + activin A + activin B + GDF-11 simultaneously. Removing all these suppressors together produces additive disinhibition of muscle mass accumulation, explaining why ACE-031 and related pan-ActRIIB approaches produced muscle effects (60% mass increase in mice; 5–9% thigh volume in Phase 1 humans) substantially larger than myostatin-specific antibodies achieved.
ACE-031’s Phase 2 DMD trial was stopped after the second dosing regimen due to epistaxis (spontaneous nosebleeds) and telangiectasias (abnormal small blood vessel formation) at higher doses. These vascular adverse events were attributed to off-target sequestration of BMP-9 and BMP-10 — vascular ligands that signal through ActRIIB-related receptors and are critical for maintaining normal vascular endothelial cell identity and arteriovenous distinction. When ACE-031 removed BMP-9/10 from circulation along with myostatin and activins, it disrupted the vascular signaling that depends on these BMPs, producing the observed vascular lesions. Acceleron Pharma and Shire permanently discontinued development in 2013. For research use, this history is important context: (1) in vivo protocols with ACE-031 should monitor for signs of vascular disruption; (2) the vascular adverse events are an intrinsic consequence of the breadth of ActRIIB ligand trapping; (3) the clinical data showing muscle volume increase remains scientifically valid and informative for muscle biology research, but the vascular liability means this specific compound is no longer in therapeutic development. Subsequent compound KER-065 specifically reduced BMP-9 affinity 400-fold to address this liability.
ACE-031 and GDF-8 are pharmacological opposites for the same pathway and form the ideal inhibitor/agonist research pair for ActRIIB/myostatin biology. GDF-8 (myostatin; YPB.233) is the endogenous ligand that activates ActRIIB → ALK4/5 → Smad2/3 phosphorylation → muscle protein synthesis suppression and satellite cell inhibition. Researchers use recombinant GDF-8 to induce the muscle atrophy/suppression state in cell culture and animal models, studying the molecular mechanisms of myostatin-driven muscle loss. ACE-031 is the pan-ActRIIB ligand trap that removes myostatin (and activin A/B and GDF-11) from the experimental system, blocking Smad2/3 signaling and releasing muscle from the suppressive state. In a complete research program, both tools together allow: (1) GDF-8 alone = confirming the Smad2/3 inhibitory pathway is intact; (2) ACE-031 alone = maximum pathway disinhibition/muscle mass stimulation; (3) GDF-8 + ACE-031 = competition assay to confirm ACE-031 neutralization of GDF-8. This agonist/antagonist toolkit is not achievable with either compound alone.
A 2025 anti-doping study analyzed 14 black-market products marketed as ACE-031 and found that none of them contained the authentic ActRIIB extracellular domain-IgG1-Fc fusion protein. Most contained full-length ActRIIB (the transmembrane receptor, not the extracellular domain Fc fusion), and many contained multiple contaminating proteins. The authentic ACE-031 is specifically the extracellular domain (not full-length receptor) fused to IgG1-Fc; this structure provides the soluble decoy receptor function and the 10–15 day half-life. Full-length ActRIIB lacks the Fc domain, would be membrane-associated rather than freely circulating, and would not function as a ligand trap. Researchers cannot verify authentic ACE-031 by HPLC purity alone: SDS-PAGE (correct molecular weight band under reducing/non-reducing conditions), Western blot with anti-ACVR2B antibody, and ideally a functional bioassay (myostatin/activin neutralization at expected EC50) are the definitive identity confirmation methods for this compound.
Yes. YourPeptideBrand.com provides white-label dropship for ACE-031 as YPB.249 (Research Use Only). White-label storefronts include pre-built RUO-compliant product pages with pan-ActRIIB ligand trap mechanism descriptions, Phase 1/2 clinical context (clearly framed as discontinued clinical research; vascular adverse events documented), WADA S4.3 classification notes, and COA library links. Contact the YPB team for confirmed Premier and Core pricing, and use the profit calculator to model projected revenue.
Every ACE-031 batch includes a lot-specific COA. Given the widespread black-market adulteration documented in 2025, the following quality parameters are particularly important: SDS-PAGE (correct molecular weight band under reducing conditions; the IgG1-Fc fusion has a characteristic gel migration pattern distinct from full-length ActRIIB or non-fusion forms); Western blot with anti-ACVR2B antibody (confirms authentic extracellular domain identity); purity (≥95% by SDS-PAGE densitometry); endotoxin (<1 EU/mg); bioburden. For critical research applications, a functional bioassay confirming myostatin neutralization (blocking GDF-8-induced Smad2/3 phosphorylation in reporter cells at expected EC50) is the gold-standard identity confirmation. All lots are traceable through the batch-specific COA library.
ACE-031 should be positioned as the reference ActRIIB pan-inhibition tool for muscle biology research — the compound with published Phase 1 human data showing 5–9% muscle volume increase, and a well-documented mechanism for studying the complete myostatin/activin/GDF-11 negative regulation axis in muscle. The clinical context (discontinued development; vascular adverse events) should be presented transparently in RUO-compliant copy — both because it is required for honest research communication and because it frames the compound’s specific research utility accurately: ACE-031 is valuable as a research tool for studying the ActRIIB pathway precisely because of its well-characterized pharmacology including both efficacy and limitations. For muscle biology research catalogs, ACE-031 (pathway inhibitor) + GDF-8 (pathway agonist) creates the most mechanistically complete ActRIIB biology toolkit available, and these two compounds serve as natural catalog companions for researchers who need to study both directions of the myostatin axis.
Key Takeaways
Research Takeaways
- Pan-ActRIIB ligand trap (not just myostatin): Sequesters GDF-8 + activin A/B + GDF-11 + BMP-2/7/9; pan-blockade > myostatin-specific inhibition (60% muscle mass increase in mice vs. lower with myostatin-only approaches; Lee et al. 2005).
- Phase 1 (Attie 2013, PMID: 23169607): 5–9% thigh muscle volume increase; T½ 10–15 days; lean mass up, fat mass down; generally well tolerated. Best human ActRIIB inhibitor class efficacy data published.
- Phase 2 DMD terminated (PMID: 27462804): Epistaxis and telangiectasias from BMP-9 vascular sequestration. All clinical development permanently discontinued 2013. Critical safety context for all in vivo protocols.
- Fusion protein, not a conventional peptide: Gentle reconstitution; low-protein-binding containers; SDS-PAGE/Western blot for identity verification; functional bioassay preferred for critical applications.
- Black-market adulteration documented (2025): All 14 tested black-market products were inauthentic; SDS-PAGE and Western blot required beyond HPLC for authentic Fc fusion identity confirmation.
- ACE-031 + GDF-8 = complete ActRIIB pathway toolkit: Inhibitor + agonist pair for directional muscle atrophy/hypertrophy research.
- WADA S4.3 Prohibited: Myostatin inhibitors category; recognized potent muscle mass effect confirmed in human data.
Business Takeaways
- Only pan-ActRIIB ligand trap in YPB catalog — unique mechanism; foundational muscle biology research tool.
- ACE-031 + GDF-8 catalog pair = complete agonist/antagonist toolkit for the ActRIIB/myostatin pathway from a single muscle biology buyer audience.
- Human Phase 1 data (5–9% muscle volume) = among the strongest evidence base for any muscle research compound in the catalog; legitimate scientific interest driver.
- Contact YPB for confirmed pricing on YPB.249.
Ready to add ACE-031 to your research catalog? Book a consultation with the YPB team.
[ypb_studies peptide=”ace-031″]