Side-by-side · Research reference

ACE-031vsTesofensine

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

APhase 2HUMAN-REVIEWED10/44 cited

BPhase 3AUTO-DRAFTED10/40 cited

ACE-031

ActRIIB-Fc Fusion · Phase 2 Halted

Phase 2Highest trial stage

2011Development halted

~58.4 kDaMolecular weightReichel 2025

SQ · Weekly dosing investigated

Tesofensine

SNDRI · Phase 3 obesity candidate

0.25–0.5 mgDaily doseAstrup 2008

9.2 kgWeight ↓ (24 wk)Astrup 2008

Phase 3Evidence levelAstrup 2008

Oral · Once daily morning

01Mechanism of Action

Parameter

ACE-031

Tesofensine

Primary target

Myostatin, GDF11, activin A — TGF-β superfamily ligands

Serotonin / norepinephrine / dopamine transporters (SERT / NET / DAT)Astrup 2008

Pathway

Soluble decoy receptor binds circulating myostatin/TGF-β ligands → prevents ActRIIB activation → SMAD2/3 pathway inhibition

Triple monoamine reuptake inhibition → ↑synaptic 5-HT, NE, DA → appetite suppression + thermogenesisAstrup 2008

Downstream effect

Disinhibition of myogenic signaling, increased skeletal muscle mass and strength

Strong appetite suppression, mild thermogenic effect, weight lossAstrup 2008

Feedback intact?

—

Origin

Recombinant fusion protein: human ActRIIB extracellular domain + IgG1-Fc fragmentReichel 2025

Small molecule developed by NeuroSearch (Denmark) for CNS indications, repurposed for obesityAstrup 2008

Antibody development

—

02Dosage Protocols

Parameter

ACE-031

Tesofensine

Clinical dosing

Weekly or biweekly SQ injections (exact doses undisclosed pre-halt)

Phase 2 DMD trial protocol not fully published.

—

Black market products

Variable purity; 12/14 tested products contained target protein plus contaminantsReichel 2025

SDS-PAGE revealed multiple protein bands; quality control absent.Reichel 2025

—

Evidence basis

Phase 2 trial discontinued — incomplete dataset

Phase 2b + ongoing Phase 3Astrup 2008

Half-life

Days to weeks (Fc-fusion typical kinetics)

IgG1-Fc domain confers extended circulation time.

~9 days (very long)

Duration investigated

12–24 weeks (trial cut short)

—

Standard dose

—

0.25–0.5 mg / dayAstrup 2008

Frequency

—

Once daily, morning

Lower / starter dose

—

0.125 mg / day

Duration

—

24 weeks per studied cycle

Form

—

Oral capsule

Timing

—

Morning to avoid sleep disruption

04Side Effects & Safety

Parameter

ACE-031

Tesofensine

Epistaxis (nosebleeds)

Significant incidence in Phase 2 DMD trial — primary safety signal

—

Telangiectasia

Dilated capillaries / spider veins observed

—

Vascular abnormalities

Mechanism: ActRIIB/ALK1 pathway disruption affects vascular homeostasis

—

Injection site reactions

Local erythema, induration (biologics class effect)

—

Antibody development

Potential for anti-drug antibodies (Fc-fusion proteins); incidence not reported

—

Black market contaminants

12/14 tested products contained multiple unidentified proteins alongside ACE-031Reichel 2025

—

Heart rate / BP

—

Dose-dependent ↑ HR + BPAstrup 2008

Insomnia

—

Dose-related; mitigate with morning timing

Dry mouth

—

Common

Nausea

—

Common

Mood changes

—

Anxiety / agitation possible

Cardiovascular events

—

Phase 3 trial monitoring; not yet FDA-cleared

Pregnancy / OB

—

Contraindicated

Absolute Contraindications

ACE-031

·History of vascular disorders (epistaxis, telangiectasia, HHT)
·Pregnancy (TGF-β pathway critical for fetal development)
·Active malignancy (myostatin inhibition may affect tumour growth)
·Use of non-pharmaceutical grade ACE-031 (contamination risk)Reichel 2025

Tesofensine

·Pregnancy / breastfeeding
·Severe cardiovascular disease
·Concurrent MAOI use

Relative Contraindications

ACE-031

·Coagulation disorders or anticoagulant use (epistaxis risk)
·Hereditary hemorrhagic telangiectasia (HHT) family history
·Cardiovascular disease (vascular remodeling effects unknown)

Tesofensine

·Hypertension
·Anxiety disorder
·Insomnia

05Administration Protocol

Parameter

ACE-031

Tesofensine

1. Pharmaceutical status

ACE-031 is not FDA-approved or commercially available. Phase 2 development was discontinued in 2011 due to safety concerns. Any ACE-031 on the black market is unregulated research chemical.

Oral capsule (investigational; not commercial).

2. Black market quality

12 of 14 tested black market ACE-031 products contained the target protein but also carried multiple unidentified protein contaminants detectable by SDS-PAGE. Two products contained no ACVR2B-immunoreactive material.Reichel 2025

Swallow whole with water, morning only.

3. Detection in sport

ACE-031 is prohibited under WADA S4.3 (Myostatin Inhibitors). Gel electrophoresis and Western blotting using ACVR2B-specific antibodies can detect the ~58.4 kDa protein in biological samples.Reichel 2025

Morning to mitigate insomnia. Do not dose evening.

4. Clinical trial route

Phase 2 protocol used subcutaneous injections at weekly or biweekly intervals. Exact dosing protocols remain unpublished.

Room temp ≤25 °C, dry place.

5. Caveat

—

Monitor BP + HR + mood. Avoid stimulants + MAOIs.