Smad3

SMAD3 is a receptor-regulated transcription factor in the TGF-β pathway, and activated TGF-β receptors phosphorylate SMAD3 to form SMAD complexes that regulate target-gene transcription^[1]. Mechanistically, SMAD3 participates in cell proliferation, apoptosis, immune suppression, epithelial-mesenchymal transition, and extracellular matrix expression, making it useful for fibrosis, cancer progression, and inflammatory signaling studies^[2]^[3]. In fibrosis models, SMAD3 acts as an important mediator of TGF-β profibrotic responses, and Smad3-deficient cells show reduced responses to selected chemotactic and matrix-related signals^[3]. In cancer, SMAD3 can function as either a negative or positive regulator of carcinogenesis depending on cell type and tumor stage^[2]. Compared with SMAD2, SMAD3 shows distinct regulation of TGF-β target genes and performs different functions in FOXH1-associated transcriptional control^[4]^[5]. For experimental applications, SIS3 selectively inhibits TGF-β1-induced SMAD3 phosphorylation and SMAD3-SMAD4 interaction, making it a practical tool for testing SMAD3-dependent mechanisms^[6].

References:

[1]. Hata A, et al. TGF-β signaling from receptors to Smads. Cold Spring Harb Perspect Biol. 2016;8(9):a022061.

[2]. Millet C, et al. Roles of Smad3 in TGF-beta signaling during carcinogenesis. Crit Rev Eukaryot Gene Expr. 2007;17(4):281-293.

[3]. Flanders KC. Smad3 as a mediator of the fibrotic response. Int J Exp Pathol. 2004;85(2):47-64.

[4]. Brown KA, et al. A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling. J Cell Biochem. 2007;101(1):9-33.

[5]. Aragón E, et al. Structural basis for distinct roles of SMAD2 and SMAD3 in FOXH1 pioneer-directed TGF-β signaling. Genes Dev. 2019;33(21-22):1506-1524.

[6]. Jinnin M, et al. Characterization of SIS3, a novel specific inhibitor of Smad3, and its effect on transforming growth factor-beta1-induced extracellular matrix expression. Mol Pharmacol. 2006;69(2):597-607. [Content Brief]

Smad3 Inhibitor (1)

Smad3 Related Products (1):

Cat. No.	Product Name	Effect	Purity

HY-147025

(S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine	Inhibitor	98.62%
(S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine is a dual target PROTAC that can not only target to the ubiquitination and degradation of Smad3 but also improve the HIF-α protein level. (S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine has a multi-path anti-fibrosis function and a renal protection function for research of renal anemia. (S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine can be used for research on prostate cancer and other cancers.

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