MUSCLE GROWTHNON-PEPTIDEResearch OnlyMYOSTATIN INHIBITORMUSCLE GROWTHNMD RESEARCH

ACE-031

Also known as: Ramatercept · ActRIIB-Fc · ACVR2B-Fc

25 views/week 198 citations 0 edits Updated 6/8/2026

ACE-031 is a soluble decoy receptor fusion protein combining the extracellular domain of activin receptor type IIB (ActRIIB) with a human Fc region. It acts as a myostatin and activin trap, producing significant lean muscle mass gains in clinical trials for neuromuscular diseases.

STRUCTURE

Molecular Composition

FORMULA

Fusion protein

MOL. WEIGHT

~100 kDa (dimer)

CAS NUMBER

N/A (biologic)

TARGET

ActRIIB (decoy receptor)

HALF-LIFE

14–25 days

STATUS

Phase 2 (paused)

AMINO ACID CHAIN VISUALIZATION

ActRIIB domain

Myostatin decoy binding

—

NH-CO

Fc region

Half-life extension

—

NH-CO

GDF-11 capture

GDF-11 sequestration

—

NH-CO

BMP-9 site

Off-target BMP binding

—

NH-CO

Smad block

Smad2/3 pathway block

SEQUENCEA-F-G-B-S

MECHANISMS

How It Works

🪤

ActRIIB Decoy Receptor Trap

ACE-031 presents a soluble, high-affinity ActRIIB extracellular domain that competes with membrane-bound ActRIIB on muscle cells. It sequesters myostatin, activin A/B, GDF-11, and BMP9 in circulation before they reach muscle tissue, functioning as a systemic ligand trap.

📈

Lean Mass Amplification

Phase 2 trials in healthy postmenopausal women showed a single 3 mg/kg dose increased lean mass by 3.3% (∼1.1 kg) within 29 days — the largest single-dose lean mass gain ever recorded in a clinical trial at that time. Muscle fibre cross-sectional area increased significantly on biopsy.

⏱️

Fc-Mediated Half-Life Extension

Fusion to the human IgG1 Fc fragment via FcRn recycling extends the half-life to 14–25 days, allowing once-weekly or biweekly dosing. This contrasts sharply with native peptide myostatin inhibitors that have half-lives of minutes.

🦴

Bone Density Secondary Effect

Phase 2 trials observed a secondary finding of significant bone mineral density increases. ActRIIB ligands (particularly activin A) suppress osteoblast activity; blocking them promotes bone formation as well as muscle growth — potentially relevant for osteoporosis.

OVERVIEW

Research Overview

ACE-031 (ramatercept) was developed by Acceleron Pharma as a treatment for neuromuscular diseases including Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). In Phase 2 trials, a single dose increased lean muscle mass by 3–5% within 29 days in healthy postmenopausal women. The programme was paused due to adverse effects including nosebleeds and gum bleeding at higher doses, likely related to off-target inhibition of BMP9/BMP10 and effects on vascular integrity.

Mechanism of Action

ACE-031 captures and sequesters myostatin (GDF-8), activin A, activin B, GDF-11, and BMP9 in circulation before they can bind endogenous ActRIIB on muscle cells. This blocks SMAD2/3 phosphorylation-mediated transcription of atrophy genes and enables sustained mTOR-driven protein synthesis and satellite cell activation.

DOSAGE

Dosage & Administration

INJECTABLE (SUBCUTANEOUS) — CLINICAL TRIAL DOSING

DOSE

1–3 mg/kg

FREQUENCY

Once every 2–4 weeks

NOTES

Long Fc-mediated half-life allows infrequent dosing. Phase 2 used single and multi-dose cohorts. Clinical programme paused — no approved dosing for human use.

Calculate dose in Peptide Calculator

ACE-031 is a research biologic with no approved therapeutic indication. The Phase 2 programme was paused due to vascular adverse effects (nosebleeds, telangiectasias) at higher doses, likely related to off-target inhibition of BMP9/BMP10, which regulate vascular endothelial integrity. Next-generation selective myostatin antibodies aim to avoid this liability.

CYCLING

Cycle Duration Guide

ON CYCLE

Single dose to 12-week course

OFF CYCLE

12+ weeks

Long half-life means effects persist 4–8 weeks after last dose. Cycling approach differs from small peptides. Clinical trials used 12-week dosing windows.

⚠

Phase 2 clinical hold. Vascular side effects at higher doses. BMP9/BMP10 inhibition may impair vascular homeostasis. Research use only with careful dose management.

View full Cycle Guide →

NOTES

Research Notes

Phase 2 clinical hold due to vascular side effects (epistaxis, telangiectasias) at higher doses. Research use only; no approved therapeutic form. Next-generation selective myostatin antibodies in development to avoid off-target BMP inhibition.

◆Quick Reference

FORMULAN/A (fusion protein)

MOL. WEIGHT100,000 Da

LENGTH0 amino acids

ORIGINRecombinant fusion protein; Acceleron Pharma

HALF-LIFE~14–25 days (Fc-mediated half-life extension)

SOLUBILITYSupplied as aqueous solution; do not freeze after reconstitution

STATUSResearch Only

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