myostatin

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Ligands
myostatin (Human)

GtoPdb Ligand ID: 5025

Synonyms: GDF-8 | GDF8 | growth/differentiation factor 8

Compound class: Endogenous peptide in human, mouse or rat

Comment: Myostatin, is a type II activin receptor ACVR2B agonist. Myostatin-induced ACVR2B activation leads to SMAD pathway signalling.
Inhibition of Myostatin/ACVR2B signalling is a mechanistic target for the development of drugs to combat muscle wasting conditions. We list three clinical stage anti-myostatin monoclonal antibodies (mAbs) in the 'Biological activity' tab for this ligand. In addition to mAbs, alternative protein scaffolds are being investigated to produce anti-myostatin activity similar to mAbs but with simpler, single-domain structures and no disulfide bonds. One such example is talditercept alfa (RO7239361, BMS-986089), which is a fusion protein that derives myostatin-binding from a modified human fibronectin domain F10. Talditercept alfa has advanced to Phase 1/2 evaluation to reduce muscle atrophy in boys with Duchenne muscular dystrophy (NCT02515669). Talditercept alfa is an example of so-called 'Adnectin' protein therapeutics that are being developed as an alternative to antigen receptors (antibodies) [5].

Species: Human

References
1. Davies J, Jones BE, Korytko AI, Mitchell PJ, Smith RC, O'Bryan LM, Wang R. (2009) Anti-myostatin antibodies. Patent number: US7632499 B2. Assignee: Eli Lilly And Company. Priority date: 12/10/2005. Publication date: 15/12/2009.
2. Donovan A, Straub M, Wawersik S. (2019) Anti-pro/latent myostatin antibodies and methods of use thereof. Patent number: WO2017120523A4. Assignee: Scholar Rock, Inc.. Priority date: 08/01/2016. Publication date: 19/10/2019.
3. Hye T, Hossain MR, Saha D, Foyez T, Ahsan F. (2023) Emerging biologics for the treatment of pulmonary arterial hypertension. J Drug Target, 31 (5): 1-15. [PMID:37026714]
4. Latres E, Pangilinan J, Miloscio L, Bauerlein R, Na E, Potocky TB, Huang Y, Eckersdorff M, Rafique A, Mastaitis J et al.. (2015) Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice. Skelet Muscle, 5: 34. [PMID:26457176]
5. Lipovsek D. (2011) Adnectins: engineered target-binding protein therapeutics. Protein Eng Des Sel, 24 (1-2): 3-9. [PMID:21068165]
6. Mader MM, Apgar JR, Parris KD. (2015) Antagonist antibodies against GDF-8 and uses therefor. Patent number: US8992913 B2. Assignee: Pfizer Inc.. Priority date: 15/06/2012. Publication date: 31/03/2015.
7. Suragani RN, Cadena SM, Cawley SM, Sako D, Mitchell D, Li R, Davies MV, Alexander MJ, Devine M, Loveday KS et al.. (2014) Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med, 20 (4): 408-14. [PMID:24658078]

References

1. Davies J, Jones BE, Korytko AI, Mitchell PJ, Smith RC, O'Bryan LM, Wang R. (2009)
Anti-myostatin antibodies.
Patent number: US7632499 B2. Assignee: Eli Lilly And Company. Priority date: 12/10/2005. Publication date: 15/12/2009.

2. Donovan A, Straub M, Wawersik S. (2019)
Anti-pro/latent myostatin antibodies and methods of use thereof.
Patent number: WO2017120523A4. Assignee: Scholar Rock, Inc.. Priority date: 08/01/2016. Publication date: 19/10/2019.

3. Hye T, Hossain MR, Saha D, Foyez T, Ahsan F. (2023)
Emerging biologics for the treatment of pulmonary arterial hypertension.
J Drug Target, 31 (5): 1-15. [PMID:37026714]

4. Latres E, Pangilinan J, Miloscio L, Bauerlein R, Na E, Potocky TB, Huang Y, Eckersdorff M, Rafique A, Mastaitis J et al.. (2015)
Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice.
Skelet Muscle, 5: 34. [PMID:26457176]

5. Lipovsek D. (2011)
Adnectins: engineered target-binding protein therapeutics.
Protein Eng Des Sel, 24 (1-2): 3-9. [PMID:21068165]

6. Mader MM, Apgar JR, Parris KD. (2015)
Antagonist antibodies against GDF-8 and uses therefor.
Patent number: US8992913 B2. Assignee: Pfizer Inc.. Priority date: 15/06/2012. Publication date: 31/03/2015.

7. Suragani RN, Cadena SM, Cawley SM, Sako D, Mitchell D, Li R, Davies MV, Alexander MJ, Devine M, Loveday KS et al.. (2014)
Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis.
Nat Med, 20 (4): 408-14. [PMID:24658078]