sotatercept

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Ligands
sotatercept

GtoPdb Ligand ID: 12962

Synonyms: ACE-011 | ACE011 | ActRIIA-IgG1 | MK-7962 | MK7962 | sotatercept-csrk | Winrevair®

sotatercept is an approved drug (EMA & FDA (2024))

Compound class: Antibody

Comment: Sotatercept (MK-7962) is a soluble activin receptor 2A (ACVR2A; ActR2) ligand trap type inhibitor. Structurally it is a fusion protein of the extracellular domain of the ActR2 and a human IgG Fc domain. In pulmonary blood vessels sotatercept sequesters ActR2 endogenous ligands (e.g. activins A and B, and growth differentiation factors 8 and 11, BMP6 and BMP7), and prevents their interaction with ActR2s to restore normal cell proliferation [3,8].

References
1. Cascino TM, Sahay S, Moles VM, McLaughlin VV. (2025) A new day has come: Sotatercept for the treatment of pulmonary arterial hypertension. J Heart Lung Transplant, 44 (1): 1-10. [PMID:39369970]
2. Humbert M, McLaughlin V, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman A, Escribano Subias P, Feldman J et al.. (2021) Sotatercept for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med, 384 (13): 1204-1215. [PMID:33789009]
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. Jain P, Materna C, Babbs K, Nurse T, Ishimwe J, Natarajan H, Joshi S, Lerner L, Fisher F, Seehra J et al.. (2024) RKER-012, a novel modified ActRIIB ligand trap, attenuated right ventricular cardiomyopathy in a preclinical model of pulmonary arterial hypertension. European Heart Journal, 45 (Supplement_1). DOI: 10.1093/eurheartj/ehae666.3360
5. Jaiswal V, Ang SP, Agrawal V, Borra V, Bandyopadhyay D, Dhakal A, DeMarco T, Fonarow GC. (2023) Sotatercept for the treatment of pulmonary arterial hypertension: a meta-analysis of randomized controlled trials. Eur Heart J Open, 3 (5): oead086. [PMID:37767012]
6. Kang C. (2024) Sotatercept: First Approval. Drugs, 84 (7): 857-862. [PMID:38904927]
7. Kopeć G. (2023) Sotatercept as a next-generation therapy for pulmonary arterial hypertension: insights from the STELLAR trial. Cardiovasc Res, 119 (16): e155-e157. [PMID:37584249]
8. Lange TJ. (2023) Refined risk stratification, current treatment, and new therapeutic approaches in pulmonary arterial hypertension. Herz, 48 (4): 259-265. [PMID:37085727]
9. Nasrollahizadeh A, Soleimani H, Nasrollahizadeh A, Hashemi SM, Hosseini K. (2024) Navigating the Sotatercept landscape: A meta-analysis of clinical outcomes. Clin Cardiol, 47 (1): e24173. [PMID:37819149]
10. O'connor-Mccourt MD, Ganesh VK, Tremblay G, Schang G. (2025) Activin receptor type iib variants and uses thereof. Patent number: WO2025019954A1. Assignee: 35Pharma Inc. Priority date: 26/07/2024. Publication date: 30/01/2025.
11. Souza R, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Waxman AB, Grünig E, Kopeć G et al.. (2023) Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial. Eur Respir J, 62 (3). [PMID:37696565]
12. Villanueva J, Wade J, Torres A, Hale G, Pham H. (2025) Sotatercept: The First FDA-Approved Activin A Receptor IIA Inhibitor Used in the Management of Pulmonary Arterial Hypertension. Am J Cardiovasc Drugs, 25 (1): 17-24. [PMID:39466552]

References

1. Cascino TM, Sahay S, Moles VM, McLaughlin VV. (2025)
A new day has come: Sotatercept for the treatment of pulmonary arterial hypertension.
J Heart Lung Transplant, 44 (1): 1-10. [PMID:39369970]

2. Humbert M, McLaughlin V, Gibbs JSR, Gomberg-Maitland M, Hoeper MM, Preston IR, Souza R, Waxman A, Escribano Subias P, Feldman J et al.. (2021)
Sotatercept for the Treatment of Pulmonary Arterial Hypertension.
N Engl J Med, 384 (13): 1204-1215. [PMID:33789009]

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. Jain P, Materna C, Babbs K, Nurse T, Ishimwe J, Natarajan H, Joshi S, Lerner L, Fisher F, Seehra J et al.. (2024)
RKER-012, a novel modified ActRIIB ligand trap, attenuated right ventricular cardiomyopathy in a preclinical model of pulmonary arterial hypertension.
European Heart Journal, 45 (Supplement_1). DOI: 10.1093/eurheartj/ehae666.3360

5. Jaiswal V, Ang SP, Agrawal V, Borra V, Bandyopadhyay D, Dhakal A, DeMarco T, Fonarow GC. (2023)
Sotatercept for the treatment of pulmonary arterial hypertension: a meta-analysis of randomized controlled trials.
Eur Heart J Open, 3 (5): oead086. [PMID:37767012]

6. Kang C. (2024)
Sotatercept: First Approval.
Drugs, 84 (7): 857-862. [PMID:38904927]

7. Kopeć G. (2023)
Sotatercept as a next-generation therapy for pulmonary arterial hypertension: insights from the STELLAR trial.
Cardiovasc Res, 119 (16): e155-e157. [PMID:37584249]

8. Lange TJ. (2023)
Refined risk stratification, current treatment, and new therapeutic approaches in pulmonary arterial hypertension.
Herz, 48 (4): 259-265. [PMID:37085727]

9. Nasrollahizadeh A, Soleimani H, Nasrollahizadeh A, Hashemi SM, Hosseini K. (2024)
Navigating the Sotatercept landscape: A meta-analysis of clinical outcomes.
Clin Cardiol, 47 (1): e24173. [PMID:37819149]

10. O'connor-Mccourt MD, Ganesh VK, Tremblay G, Schang G. (2025)
Activin receptor type iib variants and uses thereof.
Patent number: WO2025019954A1. Assignee: 35Pharma Inc. Priority date: 26/07/2024. Publication date: 30/01/2025.

11. Souza R, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Waxman AB, Grünig E, Kopeć G et al.. (2023)
Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial.
Eur Respir J, 62 (3). [PMID:37696565]

12. Villanueva J, Wade J, Torres A, Hale G, Pham H. (2025)
Sotatercept: The First FDA-Approved Activin A Receptor IIA Inhibitor Used in the Management of Pulmonary Arterial Hypertension.
Am J Cardiovasc Drugs, 25 (1): 17-24. [PMID:39466552]