TGFβ1-IN-1

TGFβ1-IN-1 is a highly effective, orally active transforming growth factor β1 (TGF-β1) specific inhibitor that can significantly block the TGF-β1 signaling pathway and inhibit the upregulation of fibrosis-related proteins (such as α-smooth muscle actin and fibronectin) mediated by it. It is suitable for the mechanism research and treatment development of fibroproliferative diseases such as liver fibrosis^[1]. TGF-β1 is a potent fibrogenic factor responsible for the synthesis of extracellular matrix and plays a key role in epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition and immunosuppressive microenvironment^{[2, 3]}.

In vitro, treatment of HK2 cells with TGFβ1-IN-1 (20μM) for 24h significantly inhibited the expression of intracellular S100 calcium-binding protein A2 (S100A2)^[4].

In vivo, oral administration of TGFβ1-IN-1 (15, 30mg/kg) to mice with carbon tetrachloride (CCl₄)-induced liver fibrosis model for 3 weeks prevented CCl₄-induced liver damage, reduced liver weight factor, serum ALT, AST, CHO and TG levels, significantly improved liver structural damage and inflammatory cell infiltration, reduced liver tissue collagen deposition, and reduced the accumulation of immune cells. The effect was better than that of Tranilast^[5].

References:
[1] Zhu J, Fan J, Xia Y, et al. Potential therapeutic targets of macrophages in inhibiting immune damage and fibrotic processes in musculoskeletal diseases[J]. Frontiers in immunology, 2023, 14: 1219487.
[2] Laping N J, Grygielko E, Mathur A, et al. Inhibition of transforming growth factor (TGF)-β1–induced extracellular matrix with a novel inhibitor of the TGF-β type I receptor kinase activity: SB-431542[J]. Molecular pharmacology, 2002, 62(1): 58-64.
[3] Chung J Y F, Chan M K K, Li J S F, et al. TGF-β signaling: from tissue fibrosis to tumor microenvironment[J]. International Journal of Molecular Sciences, 2021, 22(14): 7575.
[4] Yang X, Zheng F, Yan P, et al. S100A2 activation promotes interstitial fibrosis in kidneys by FoxO1-mediated epithelial-mesenchymal transition[J]. Cell Biology and Toxicology, 2024, 40(1): 86.
[5] Yue L, Xue T, Su X, et al. Discovery and evaluation of phenacrylanilide derivatives as novel potential anti-liver fibrosis agents[J]. European journal of medicinal chemistry, 2022, 242: 114685.

TGFβ1-IN-1是一种高效、具口服活性的转化生长因子β1（TGF-β1）特异性抑制剂，能够显著阻断TGF-β1信号通路，抑制其介导的纤维化相关蛋白（如α-平滑肌肌动蛋白和纤连蛋白）的表达上调，适用于肝纤维化等纤维增生性疾病的机制研究与治疗开发^[1]。TGF-β1是一种强效的纤维化因子，负责细胞外基质的合成，在上皮-间质转化（EMT）、细胞外基质（ECM）沉积和免疫抑制微环境中起关键作用^{[2, 3]}。

在体外，TGFβ1-IN-1（20μM）处理HK2细胞24h，显著抑制了细胞内S100钙结合蛋白A2（S100A2）的表达^[4]。

在体内，TGFβ1-IN-1（15, 30mg/kg）通过口服治疗四氯化碳（CCl₄）诱导的肝纤维化模型小鼠3周，预防了CCl₄诱导的肝损伤，降低了肝重量因子、血清ALT、AST、CHO和TG水平，显著改善了肝脏结构损伤和炎性细胞浸润，减少了肝组织胶原沉积，减少了免疫细胞的积聚，效果比曲尼司特（Tranilast）更好^[5]。