Department of Cardiovascular Medicine, Second Xiangya Hospital of Central South University, Changsha 410011, China; Xiangya School of Medicine, Central South University, Changsha 410013, China.
Department of Hematology, Second Xiangya Hospital of Central South University, Changsha 410011, China.
Biomed Pharmacother. 2023 Sep;165:115239. doi: 10.1016/j.biopha.2023.115239. Epub 2023 Jul 27.
Sotatercept (ACE-011) is an activin receptor IIA-Fc (ActRIIA-Fc) fusion protein currently under investigation for its potential in the treatment of hematologic diseases. By impeding the activities of the overexpressed growth and differentiation factor 11 (GDF11), activin A, and other members of the transforming growth factor-β (TGF-β) superfamily, commonly found in hematologic disorders, sotatercept aims to restore the normal functioning of red blood cell maturation and osteoblast differentiation. This action is anticipated to enhance anemia management and hinder the progression of myeloma. Simultaneously, comprehensive research is ongoing to investigate sotatercept's pharmacokinetics and potential adverse reactions, thus laying a robust foundation for its prospective clinical use. In this review, we provide a detailed overview of TGF-β pathways in physiological and hematologic disorder contexts, outline the potential mechanism of sotatercept, and delve into its pharmacokinetics and clinical research advancements in various hematologic diseases. A particular emphasis is given to the relationship between sotatercept dosage and its efficacy or associated adverse reactions.
索特西普（ACE-011）是一种激活素受体 IIA-Fc（ActRIIA-Fc）融合蛋白，目前正在研究其在血液疾病治疗方面的潜力。通过抑制过度表达的生长分化因子 11（GDF11）、激活素 A 和其他转化生长因子-β（TGF-β）超家族成员的活性，这些因子通常存在于血液疾病中，索特西普旨在恢复红细胞成熟和破骨细胞分化的正常功能。这一作用预计将改善贫血的管理并阻止骨髓瘤的进展。同时，正在进行全面的研究以调查索特西普的药代动力学和潜在的不良反应，从而为其未来的临床应用奠定坚实的基础。在这篇综述中，我们详细介绍了 TGF-β 途径在生理和血液疾病背景下的作用，概述了索特西普的潜在作用机制，并深入探讨了其在各种血液疾病中的药代动力学和临床研究进展。特别强调了索特西普剂量与其疗效或相关不良反应之间的关系。
