1. Stem Cell/Wnt TGF-beta/Smad
  2. TGF-β Receptor TGF-beta/Smad
  3. Sotatercept (mIgG2a)

Sotatercept (mIgG2a)  (Synonyms: RAP-011)

Cat. No.: HY-P99590A Purity: 99.71%
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Sotatercept (mIgG2a) (RAP-011), the murine homolog of Sotatercept (ACE-011) (HY-P99590), 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).

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Based on 1 publication(s) in Google Scholar

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Description

Sotatercept (mIgG2a) (RAP-011), the murine homolog of Sotatercept (ACE-011) (HY-P99590), 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].

Isotype

Mouse IgG2a kappa

Recommend Isotype Controls
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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

RT-PCR[1]

Cell Line: K562 cells
Concentration: 0.05 g/L with 50 ng/mL GDF11
Incubation Time: 5 d
Result: Significantly upregulated the erythroid differentiation markers (such as KLF1, ABCB6, etc.).
Upregulated the anti-apoptotic gene BCL2 and downregulated the pro-apoptotic genes BAX/BAD.
Significantly reduced the expression of mRNA ERFE.

Western Blot Analysis[1]

Cell Line: K562 cells
Concentration: 0.05 g/L with 50 ng/mL GDF11
Incubation Time: 0.5, 1, 2 h
Result: Significantly inhibited the phosphorylation of SMAD2 induced by GDF1.
Promoted the nuclear translocation of GATA1, accompanied by an increase in nuclear expression of HSP70 and a decrease in nuclear expression of SMAD4.
Significantly reduced the expression of ERFE protein.
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 (HY-P70409) 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Closed femoral fracture surgery established in 8-week male Wistar rats[2]
Dosage: 0.6 mg/kg biw (x 2 doses) + 0.35 mg/kg biw (x 3 doses); 0.18 mg/kg biw (x2 doses) + 0.1 mg/kg biw (x 7 doses) and 10mg/kg biw (x 12 doses)
Administration: Subcutaneous injection (s.c.), twice a week for 2-6 weeks
Result: Significantly increased callus length and bone volume at high-dose RAP-011 (10mg/kg biw), but the quality of the newly formed bone tissue was relatively low, and the improvement in mechanical properties was limited.
Demonstrated certain anabolic effects at low-dose pulsed administration.
No obvious effect at continuous low-dose administration.
Animal Model: Iron-deficiency anemia model established in C57BL/6 mice and in hepcidin antimicrobial peptide over expressing mice (Tg-Hamp mice)[3]
Dosage: 30 mg/kg
Administration: Intraperitoneal injection (i.p.), once daily for 10 days
Result: Significantly increase the hemoglobin concentration in both wild-type and Tg-Hamp mice (better).
Promoted the production of red blood cells while not causing excessive depletion of iron reserves.
Significantly increased the proportion of late erythroid precursor cells (the CD44low population).
Did not change the expression level of Hamp.
Animal Model: CKD that stimulated atherosclerotic calcification model established in high fat fed ldlr−/− mice[4]
Dosage: 10 mg/kg
Administration: Subcutaneous injection (s.c.), twice weekly for 6 weeks
Result: Reduced the calcium content and calcium deposits in the aortal.
Increased the markers of vascular smooth muscle (sm22α, αSMA) and reduced osteogenic markers (Runx2, alkaline phosphatase).
Restored the ActRIIA signal and regulated the Wnt signal.
Inhibited fibrosis mediated by Smad, increased the expression of klotho and downregulated the Wnt/Dkk1 signaling pathway.
Application

ELISA, FACS, Functional assay

Conjugated

Unconjugated

Reconsititution

The product can be reconstituted/diluted with sterile PBS or saline.

Molecular Weight

79.67 kDa

Appearance

Liquid

Color

Colorless to light yellow

SMILES

[Sotatercept (mIgG2a)]

Shipping

Shipping with dry ice.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Biological Activity
  • Immobilized Biotinylated Activin A Protein, Mouse (HY-P73241) can bind Sotatercept (mIgG2a). The EC50 for this effect is 472.2 ng/mL.
Purity & Documentation
References
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Product Name:
Sotatercept (mIgG2a)
Cat. No.:
HY-P99590A
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