Bimagrumab
Bimagrumab is a monoclonal antibody targeting activin type II receptors (ActRII). Bimagrumab binds to human ActRIIB (Kd 1.7 pM) and ActRIIA (Kd 434 pM), blocks ligand binding and downstream Smad activation, and inhibits myostatin/activin A-induced Smad phosphorylation. The Fc region of Bimagrumab incorporates L234A and L235A mutations, which are designed to reduce the antibody's binding to FcγR and C1q, thereby attenuating or eliminating its ADCC (antibody-dependent cell-mediated cytotoxicity) and CDC (complement-dependent cytotoxicity) effector functions. Bimagrumab induces skeletal muscle hypertrophy in an Akt-independent manner via mTOR-mediated muscle protein synthesis, increases muscle mass and strength, promotes myoblast differentiation/fusion, prevents myotube atrophy and glucocorticoid-induced muscle loss, reduces fat mass and fat depot weight/adipocyte size, inhibits adipose inflammation, induces fat oxidation, preserves lean body mass during incretin-induced weight loss, and enhances the appetite-suppressive effect of incretins. Bimagrumab can be used in research on obesity and skeletal muscle atrophy and weakness.
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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- Pureté et documentation
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Activité biologique
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| HEK-293T | IC50 |
154 pM
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Inhibition of myostatin-induced Smad2/3 CAGA12-luciferase reporter signaling in HEK293T cells incubated 24 hrs.
Inhibition of myostatin-induced Smad2/3 CAGA12-luciferase reporter signaling in HEK293T cells incubated 24 hrs.
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24298022 |
| HEK-293T | IC50 |
343 pM
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Inhibition of activin A-induced Smad2/3 CAGA12-luciferase reporter signaling in HEK293T cells incubated 24 hrs.
Inhibition of activin A-induced Smad2/3 CAGA12-luciferase reporter signaling in HEK293T cells incubated 24 hrs.
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24298022 |
| Myoblast | IC50 |
519 pM
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Relief of myostatin-induced inhibition of differentiation in primary human skeletal myoblasts assessed by CK activity.
Relief of myostatin-induced inhibition of differentiation in primary human skeletal myoblasts assessed by CK activity.
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24298022 |
| Myoblast | IC50 |
3105 pM
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Relief of activin A-induced inhibition of differentiation in primary human skeletal myoblasts assessed by CK activity.
Relief of activin A-induced inhibition of differentiation in primary human skeletal myoblasts assessed by CK activity.
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24298022 |
In Vitro
Bimagrumab (4 days) enhances primary human skeletal myoblast differentiation and reverses myostatin/activin A inhibition, with IC50 values of 519 pM and 3,105 pM in the CK differentiation assay[4].
Bimagrumab (30 μg/mL; 2-72 h) prevents myostatin- and activin A-induced atrophy and Smad2/3 activation in human primary myotubes[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Bimagrumab (20 mg/kg; i.p.; once weekly; 3 weeks) increases 3-week weight loss to -14.5 g and achieves 96.4% weight-loss quality when added to Tirzepatide (HY-P1731) in diet-induced obese mice[3].
Bimagrumab (20 mg/kg; i.p.; once weekly; 3 weeks) increases 3-week weight loss to -9.8 g and achieves 104.6% weight-loss quality when added to Semaglutide in diet-induced obese mice[3].
Bimagrumab (20 mg/kg; i.p.; once weekly; 3 weeks) increases 3-week weight loss to -4.5 g and achieves 122.8% weight-loss quality when added to liraglutide in diet-induced obese mice[3].
Bimagrumab (20 mg/kg; s.c.; days 0, 7, 14, 21, and 28) increases body weight, lean mass, and muscle weight in wild-type mice[4].
Bimagrumab (20 mg/kg; s.c.; days 0, 7, 14, 21, and 28) increases body weight, lean mass, and muscle weight in myostatin-deficient MstnLn/Ln mice[4].
Bimagrumab (5-20 mg/kg; i.p.; days 21, 23, and 28) enhances recovery from glucocorticoid-induced skeletal muscle atrophy in mice[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57Bl/6J background (male, 24-25 weeks, diet-induced obese)[1]
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Dosage:20 mg/kg
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Administration:s.c.; once weekly; 14 days
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Result:Decreased fat mass by approximately 30% and increased lean mass by approximately 8%.
At day 14, adipose depot weights were iWAT 1.339 g, eWAT 1.122 g, rpWAT 0.481 g, and BAT 0.281 g.
Average adipocyte size was decreased in iWAT and eWAT.
Skeletal muscle weights were TA 64.39 mg, EDL 16.89 mg, soleus 12.89 mg, and gastrocnemius 202.44 mg.
Skeletal muscle size increased by approximately 10-20% across all four muscles.
TA muscle fiber cross-sectional area was larger than in control mice.
Fed blood glucose was modestly elevated, plasma insulin trended lower, adiponectin was comparable, leptin trended lower, IL-6 and MCP-1 trended lower, and circulating glycerol and free fatty acids were reduced.
Exercise performance showed VO2 max 4.83 mL/min (18% improvement) and time to exhaustion 682.0 s; the VO2 max effect was lean-mass dependent by ANCOVA.
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Animal Model:C57Bl/6J background (male, 24-25 weeks, diet-induced obese)[1]
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Dosage:20 mg/kg
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Administration:s.c.; once weekly (bimagrumab); once daily (semaglutide); 14 days
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Result:Combination administration produced greater than 25% body weight loss and 70% fat mass loss.
Lean mass proportion was indistinguishable from control at day 13, indicating preservation of lean mass despite reduced food intake.
At day 14, adipose depot weights were iWAT 0.606 g, eWAT 0.589 g, rpWAT 0.203 g, and BAT 0.174 g; eWAT, iWAT, and rpWAT showed greater than 60% reductions relative to control.
Adipocyte size was smallest in the combination group.
Skeletal muscle weights were TA 58.69 mg, EDL 14.88 mg, soleus 11.38 mg, and gastrocnemius 184.63 mg, comparable to control.
Adiponectin increased compared with semaglutide alone, leptin decreased compared with control, IL-6 and MCP-1 trended lower, and circulating glycerol and free fatty acids were reduced.
Exercise performance showed VO2 max 4.61 mL/min (13% average improvement) and time to exhaustion 760.5 s.
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Animal Model:Akt1 loxp/loxp;Akt2 loxp/loxp with ACTA1-Cre (M-AktDKO; male, 4-6 months) and control mice[1]
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Dosage:20 mg/kg
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Administration:s.c.; once weekly; 14 days
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Result:In control mice, TA, EDL, soleus, and gastrocnemius weights increased to 52.64 mg, 12.61 mg, 7.89 mg, and 148.5 mg, respectively.
In M-AktDKO mice, TA, EDL, soleus, and gastrocnemius weights were 32.52 mg, 8.43 mg, 5.58 mg, and 99.41 mg, respectively; EDL and gastrocnemius were larger than in M-AktDKO mice, and TA and soleus trended larger.
The percent increase in muscle weights was 17-27% in control mice and 11-23% in M-AktDKO mice.
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Animal Model:C57BL/6J (5-6 weeks of age at diet initiation; average body weight 54 g at start of dosing)[3]
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Dosage:20 mg/kg
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Administration:i.p. once weekly for 3 weeks; s.c. daily for 3 weeks
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Result:Three-week weight loss increased to -14.5 g when combined with tirzepatide.
Weight-loss quality in combination was 96.4%.
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Animal Model:C57BL/6J (5-6 weeks of age at diet initiation; average body weight 54 g at start of dosing)[3]
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Dosage:20 mg/kg
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Administration:i.p. once weekly for 3 weeks; s.c. daily for 3 weeks
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Result:Three-week weight loss increased to -9.8 g when combined with semaglutide.
Weight-loss quality in combination was 104.6%.
Fat mass loss greater than 100% of total weight loss reflected additive fat mass loss and muscle mass gain.
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Animal Model:C57BL/6J (5-6 weeks of age at diet initiation; average body weight 54 g at start of dosing)[3]
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Dosage:20 mg/kg
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Administration:i.p. once weekly for 3 weeks; s.c. twice daily for 3 weeks
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Result:Three-week weight loss increased to -4.5 g when combined with liraglutide.
Weight-loss quality in combination was 122.8%.
Fat mass loss greater than 100% of total weight loss reflected additive fat mass loss and muscle mass gain.
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Animal Model:CB17/ICR-Prkdcscid/Crl (SCID; female; 10 weeks old)[4]
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Dosage:6 mg/kg; 20 mg/kg
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Administration:s.c.; once weekly; 4 weeks
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Result:Increased body weight and skeletal muscle mass in all examined muscles, including slow, fast, and mixed muscles, in a dose-dependent manner.
Maximal muscle increases reached 25% to 50% depending on the muscle.
The fiber cross-sectional area distribution of gastrocnemius/plantaris increased, reflecting increased individual fiber diameter without changes in fiber number.
Fiber type composition was not altered.
Microarray analysis after 4 weeks at 20 mg/kg identified 58 differentially regulated genes: 47 upregulated and 11 downregulated.
Igf1 was upregulated with a log2 fold change of 0.98 (Table 1).
Pathway analysis suggested extracellular matrix remodeling and downregulation of translation and oxidative phosphorylation.
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Animal Model:C57BL/6J (wild-type; male; 15 to 20 weeks old)[4]
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Dosage:20 mg/kg
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Administration:s.c.; days 0, 7, 14, 21, and 28
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Result:Increased body weight, lean body mass, and muscle weight in wild-type mice.
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Animal Model:C57BL/6J-Mstnlean/J (MstnLn/Ln; male; 15 to 20 weeks old)[4]
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Dosage:20 mg/kg
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Administration:s.c.; days 0, 7, 14, 21, and 28
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Result:Increased body weight, lean body mass, and muscle weight in MstnLn/Ln mice.
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Animal Model:C57BL/6 (male; 4 months old)[4]
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Dosage:5 mg/kg/week; 20 mg/kg/week; 5 or 20 mg/kg (i.p.; days 0, 2, and 7)
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Administration:s.c.; weekly; 14 days; i.p. on days 0, 2, and 7
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Result:Prevented dexamethasone-induced loss of muscle mass, tetanic force, and fiber cross-sectional area.
Dexamethasone-induced tetanic force loss of more than 20% was fully reversed.
Reduced dexamethasone-induced MAFbx and MuRF1 mRNA expression.
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Animal Model:C57BL/6 (male; 4 months old)[4]
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Dosage:5 mg/kg; 20 mg/kg
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Administration:i.p.; days 21, 23, and 28
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Result:Recovery of skeletal muscle mass in gastrocnemius/plantaris and tibialis cranialis muscles was dose-dependently enhanced after 3 weeks of dexamethasone exposure and dexamethasone withdrawal.
- Kinase activity and phosphorylation assays
- Western Blot
- Cell Cytotoxicity Assay
- Mammalian live/dead viability and cytotoxicity staining
- Research Protocol for Endocrine Diseases
- Large-size fat particle sorting
- C2C12 myoblast-to-myotube differentiation
- Protocol for Kinase activity and phosphorylation assays
- Research Protocol for Inflammation-related Diseases
- Research Protocol for Metabolic Diseases
- Cell Viability Determination by MTT Colorimetric Assay
Chemical Information
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SMILES
[Bimagrumab]
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Nunn E, et al. Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism. Molecular metabolism. 2024 Feb;80:101880. [Content Brief]
[2]. Kaiser M, et al. Bimagrumab: Novel Medical Therapy for Inclusion Body Myositis, Sarcopenia, and Medication-Induced Lean Body Mass Loss. Cardiology in review. 2025 Nov 03. [Content Brief]
[4]. Lach-Trifilieff E, et al. An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy. Molecular and cellular biology. 2014 Feb;34(4):606-18. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Bimagrumab Related Classifications
HY-P99355A Related Classifications
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