ITD 1 is a selective TGFβ receptor inhibitor (IC50 = 460nM) [1]. ITD 1 promotes the differentiation of stem cells into cardiomyocytes by inhibiting the Wnt/β-catenin signaling pathway [2]. ITD 1 is used in basic research such as cardiac regeneration [3-4].
In U87 and U251 cells, cell proliferation was inhibited after ITD 1 (5μM; 24h) treatment [5]. In human fibroblasts, inhibition of TβRII by ITD 1 (5μM; 24h) under hypoxic conditions reduces p-Smad2/3 levels and collagen deposition [6]. In human corneal endothelial cells, ITD 1 (10μM; 48h) inhibits cell proliferation, accelerates senescence, and reduces the expression of endothelial cell markers [7].
In C57BL/6J mice, ITD 1 (20μL; 2000ng; im; 4d) reduced TGF-β activity in muscle [8]. In Lewis cell subcutaneous tumor mouse model, ITD 1 (5mg/kg; ip; 5d) weakened SAHA-induced anti-tumor immunity and CD8+ T cell activation by inhibiting Smad2/3 signaling [9].
References:
[1]. Willems E, Cabral-Teixeira J, Schade D, et al. Small molecule-mediated TGF-β type II receptor degradation promotes cardiomyogenesis in embryonic stem cells[J]. Cell stem cell, 2012, 11(2): 242-252.
[2]. Zhong Q, Laco F, Liao M C, et al. Influencing the fate of cardiac and neural stem cell differentiation using small molecule inhibitors of alk5[J]. Stem cells translational medicine, 2018, 7(10): 709-720.
[3]. Plowright A T, Engkvist O, Gill A, et al. Heart regeneration: opportunities and challenges for drug discovery with novel chemical and therapeutic methods or agents[J]. Angewandte Chemie International Edition, 2014, 53(16): 4056-4075.
[4]. Lin Y H, Kang L, Feng W H, et al. Effects of lipids and lipoproteins on mesenchymal stem cells used in cardiac tissue regeneration[J]. International journal of molecular sciences, 2020, 21(13): 4770.
[5]. Sun Z, Yan T, Jiang H, et al. Claudin-3 facilitates the progression and mediates the tumorigenic effects of TGF-β in glioblastoma multiforme[J]. Medical Oncology, 2023, 40(9): 268.
[6]. Mingyuan X, Qianqian P, Shengquan X, et al. Hypoxia-inducible factor-1α activates transforming growth factor-β1/Smad signaling and increases collagen deposition in dermal fibroblasts[J]. Oncotarget, 2017, 9(3): 3188.
[7]. Ozen E A, Toprak E K, Donmez A Ç, et al. Investigation of the Effects of TGF-β and TGF-β Inhibitors on Cell Proliferation and Senescence in Human Corneal Endothelial Cells[J]. Acta Physiologica, 2023, 237.
[8]. Mázala D A G, Novak J S, Hogarth M W, et al. TGF-β–driven muscle degeneration and failed regeneration underlie disease onset in a DMD mouse model[J]. Jci Insight, 2020, 5(6): e135703.
[9]. Dong W, He B, Cao Y, et al. Low-dose SAHA enhances CD8+ T cell-mediated antitumor immunity by boosting MHC I expression in non-small cell lung cancer[J]. Cellular Oncology, 2025, 48(1): 249-264.
ITD 1是一种选择性TGFβ受体抑制剂（IC50 = 460nM） [1]。ITD 1通过抑制Wnt/β-catenin信号通路促进干细胞向心肌细胞分化 [2]。ITD 1已用于心脏再生等基础研究 [3-4]。
在U87和U251细胞中，ITD 1（5μM；24h）处理后细胞增殖受到抑制 [5]。在人成纤维细胞中，低氧条件下ITD 1（5μM；24h）抑制TβRII可降低p-Smad2/3水平和胶原沉积 [6]。在人角膜内皮细胞中，ITD 1（10μM；48h）可抑制细胞增殖，加速衰老，并降低内皮细胞标志物的表达 [7]。
在C57BL/6J小鼠中，ITD 1（20μL；2000ng；im；4d）降低了肌肉中TGF-β的活性 [8]。在Lewis细胞皮下肿瘤小鼠模型中，ITD 1（5mg/kg；ip；5d）通过抑制Smad2/3信号传导减弱了SAHA诱导的抗肿瘤免疫和CD8+T细胞活化 [9]。