Sotatercept (mIgG2a) (RAP-011), the murine homolog of Sotatercept (ACE-011), is a soluble activin receptor type IIA ( ActRIIA ) ligand trap. Sotatercept (mIgG2a) inhibits the binding of activin A and other members of the TGF-β superfamily (such as Activin A/B, GDF11 and BMP9/10) to their receptors by combining and neutralizing them, thereby regulating cell proliferation and differentiation. Sotatercept (mIgG2a) mainly inhibits the SMAD2/3 signaling pathway, and can be used in various diseases such as chronic kidney disease. Sotatercept (mIgG2a) reduces the expression of erythropoietic hepcidin ( ERFE ), regulates iron metabolism, and promotes red blood cell production. Sotatercept (mIgG2a) has a dual effect of promoting bone formation (anabolic) and inhibiting bone resorption (catabolic) [1] [2] [3] [4].
In Vivo, Sotatercept (mIgG2a) (0.1-10 mg/kg, s.c., twice a week for 2-6 weeks) is effective in promoting bone formation during repair in rats[2]. Sotatercept (mIgG2a) (30 mg/kg, i.p., once daily for 10 days) shows a significant effect in stimulating red blood cell production in Hamp transgenic mice, while avoiding the common problem of iron depletion that occurs in Erythropoietin treatment[3]. Sotatercept (mIgG2a) (10 mg/kg, s.c., twice a week for 6 weeks) protects against vascular calcification and renal fibrosis in chronic kidney disease (CKD) mice model[4].
In Vitro, Sotatercept (mIgG2a) (0.05 g/L, 1 h- 5 d) inhibits SMAD2 phosphorylation and ERFE expression, induces nuclear translocation of the transcription factor GATA1 and restores gene expression of erythroid markers[1].
References:
[1]. De Rosa G, et al. RAP-011 Rescues the Disease Phenotype in a Cellular Model of Congenital Dyserythropoietic Anemia Type II by Inhibiting the SMAD2-3 Pathway. Int J Mol Sci. 2020 Aug 4;21(15):5577.
[2]. Morse A, et al. RAP-011 augments callus formation in closed fractures in rats. J Orthop Res. 2016 Feb;34(2):320-30.
[3]. Langdon JM, et al. RAP-011, an activin receptor ligand trap, increases hemoglobin concentration in hepcidin transgenic mice. Am J Hematol. 2015 Jan;90(1):8-14.
[4]. Agapova OA, et al. Ligand trap for the activin type IIA receptor protects against vascular disease and renal fibrosis in mice with chronic kidney disease. Kidney Int. 2016 Jun;89(6):1231-43.
In Vivo, Sotatercept (mIgG2a) (0.1-10 mg/kg, s.c., twice a week for 2-6 weeks) is effective in promoting bone formation during repair in rats[2]. Sotatercept (mIgG2a) (30 mg/kg, i.p., once daily for 10 days) shows a significant effect in stimulating red blood cell production in Hamp transgenic mice, while avoiding the common problem of iron depletion that occurs in Erythropoietin treatment[3]. Sotatercept (mIgG2a) (10 mg/kg, s.c., twice a week for 6 weeks) protects against vascular calcification and renal fibrosis in chronic kidney disease (CKD) mice model[4].
In Vitro, Sotatercept (mIgG2a) (0.05 g/L, 1 h- 5 d) inhibits SMAD2 phosphorylation and ERFE expression, induces nuclear translocation of the transcription factor GATA1 and restores gene expression of erythroid markers[1].
References:
[1]. De Rosa G, et al. RAP-011 Rescues the Disease Phenotype in a Cellular Model of Congenital Dyserythropoietic Anemia Type II by Inhibiting the SMAD2-3 Pathway. Int J Mol Sci. 2020 Aug 4;21(15):5577.
[2]. Morse A, et al. RAP-011 augments callus formation in closed fractures in rats. J Orthop Res. 2016 Feb;34(2):320-30.
[3]. Langdon JM, et al. RAP-011, an activin receptor ligand trap, increases hemoglobin concentration in hepcidin transgenic mice. Am J Hematol. 2015 Jan;90(1):8-14.
[4]. Agapova OA, et al. Ligand trap for the activin type IIA receptor protects against vascular disease and renal fibrosis in mice with chronic kidney disease. Kidney Int. 2016 Jun;89(6):1231-43.