Bimagrumab: Molecular Structure
Chemical properties, amino acid sequence, and structural analysis
📌TL;DR
- •Molecular formula: Complex immunoglobulin
- •Molecular weight: 145000 Da
- •Half-life: Approximately 19 days in humans, consistent with typical IgG1 monoclonal antibody pharmacokinetics. This long half-life supports dosing intervals of every 4 weeks in clinical trials.
Amino Acid Sequence
134 amino acids
Formula
Complex immunoglobulin
Molecular Weight
145000 Da
Half-Life
Approximately 19 days in humans, consistent with typical IgG1 monoclonal antibody pharmacokinetics. This long half-life supports dosing intervals of every 4 weeks in clinical trials.
Molecular Structure#
Bimagrumab is a full-length monoclonal antibody, fundamentally different from the small peptides that comprise most entries on this site. It is included here because of its relevance to the myostatin/activin signaling pathway shared with other musculoskeletal peptides.
Antibody Architecture#
| Property | Value |
|---|---|
| Type | Fully human IgG1/lambda monoclonal antibody |
| Molecular weight | ~145,000 Da (145 kDa) |
| Heavy chains | 2 x 445 amino acids (gamma-1) |
| Light chains | 2 x 217 amino acids (lambda) |
| Total amino acids | ~1,324 |
| Glycosylation | Yes (N-linked, typical IgG1 pattern) |
| Target | Activin type II receptors (ActRIIA and ActRIIB) |
Size Comparison#
| Molecule | Type | Molecular Weight |
|---|---|---|
| Bimagrumab | IgG1 monoclonal antibody | ~145,000 Da |
| Follistatin-344 | Glycoprotein | ~38,000 Da |
| ACE-031 (ramatercept) | ActRIIB-Fc fusion protein | ~90,000 Da |
| Myostatin (GDF-8) | Homodimer | ~25,000 Da |
| BPC-157 | Pentadecapeptide | ~1,419 Da |
At 145 kDa, bimagrumab is approximately 100 times larger than a typical small peptide and can only be produced through recombinant protein expression in mammalian cell systems.
Binding Properties#
Receptor Specificity#
Bimagrumab binds competitively to both activin type II receptors at the critical myostatin/activin binding site:
| Receptor | Binding Affinity | Relative Preference |
|---|---|---|
| ActRIIB | Subnanomolar | Primary target (>200-fold preference) |
| ActRIIA | Subnanomolar | Secondary target |
The dual receptor binding is significant because both ActRIIA and ActRIIB contribute to myostatin and activin signaling in skeletal muscle. Blockade of both receptors may produce more complete inhibition of the atrophy pathway than targeting a single receptor.
Ligand Blockade#
By occupying the ligand binding site on ActRII, bimagrumab prevents signaling by multiple TGF-beta superfamily members:
| Ligand Blocked | Normal Function | Effect of Blockade |
|---|---|---|
| Myostatin (GDF-8) | Limits muscle growth | Muscle hypertrophy |
| Activin A | Promotes muscle atrophy, fat deposition | Preserved muscle, reduced fat |
| GDF-11 | Aging and tissue homeostasis | Uncertain |
| BMP-9/10 | Angiogenesis regulation | Potential off-target effects |
Pharmacokinetics#
Half-Life and Dosing#
The approximately 19-day half-life is characteristic of IgG1 monoclonal antibodies, which benefit from FcRn-mediated recycling that protects them from lysosomal degradation. This long half-life supports:
- Every 4-week (Q4W) dosing in clinical trials
- Gradual accumulation to steady state over multiple doses
- Sustained receptor occupancy between doses
Administration#
Bimagrumab is administered as an intravenous (IV) infusion, unlike most peptides which are given subcutaneously. IV administration is necessary for this large protein to ensure complete bioavailability and precise dosing.
Production#
As a full-length human monoclonal antibody, bimagrumab is produced through recombinant DNA technology using mammalian cell expression systems (typically CHO cells). This manufacturing process:
- Requires sophisticated bioreactor systems
- Involves extensive purification (protein A chromatography, ion exchange, viral inactivation)
- Must maintain consistent glycosylation patterns
- Operates under strict GMP conditions
- Cannot be synthesized using standard peptide synthesis methods
This production complexity distinguishes bimagrumab from small peptides that can be made via solid-phase peptide synthesis.
Related Reading#
Frequently Asked Questions About Bimagrumab
What type of peptide is Bimagrumab?
Bimagrumab (BYM338) is a fully human IgG1 monoclonal antibody that blocks activin type II receptors (ActRIIA and ActRIIB), inhibiting myostatin, activin A, and other TGF-beta superfamily ligands that suppress muscle growth. Originally developed by Novartis, licensed to Versanis Bio, then acquired by Eli Lilly for up to $1.925 billion in 2023. Phase 2 trials demonstrated simultaneous fat mass loss (20.5%) and lean mass gain (3.6%) in adults with type 2 diabetes and obesity. The BELIEVE Phase 2b trial showed the bimagrumab-semaglutide combination preserved 67% more lean mass than semaglutide alone while achieving 22.1% total weight loss. Not yet approved by any regulatory agency.
What is the half-life of Bimagrumab?
The reported half-life of Bimagrumab is Approximately 19 days in humans, consistent with typical IgG1 monoclonal antibody pharmacokinetics. This long half-life supports dosing intervals of every 4 weeks in clinical trials.. Half-life can vary depending on the route of administration, formulation, and individual factors. This information is based on available preclinical or pharmacokinetic data.
What is the amino acid sequence of Bimagrumab?
The amino acid sequence of Bimagrumab is Full-length IgG1 monoclonal antibody with 2 heavy chains (445 amino acids each) and 2 light chains (217 amino acids each, lambda type). Bimagrumab is a fully human IgG1/lambda monoclonal antibody with a molecular weight of approximately 145 kDa. It consists of two identical heavy chains (gamma-1, 445 amino acids each) and two identical light chains (lambda, 217 amino acids each) connected by disulfide bonds. The antibody binds competitively to activin type II receptors (ActRIIA and ActRIIB) at the myostatin/activin binding site, with greater than 200-fold binding preference for ActRIIB.. This sequence determines its biological activity and binding properties.
How stable is Bimagrumab in storage?
Bimagrumab is typically supplied as a lyophilized powder for maximum stability. Bimagrumab is a fully human IgG1/lambda monoclonal antibody with a molecular weight of approximately 145 kDa. It consists of two identical heavy chains (gamma-1, 445 amino acids each) and two identical light chains (lambda, 217 amino acids each) connected by disulfide bonds. The antibody binds competitively to activin type II receptors (ActRIIA and ActRIIB) at the myostatin/activin binding site, with greater than 200-fold binding preference for ActRIIB.. When reconstituted, it should be stored refrigerated at 2-8 degrees C and protected from light. Lyophilized powder should be stored at -20 degrees C.
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