Disitertide (P144) is a specific inhibitor of transforming growth factor β1 (TGF-β1) receptor type I [1]. Disitertide binds to the TGF-β1 receptor, blocking the TGF-β1 signaling pathway and inhibiting extracellular matrix deposition and fibrotic responses, thereby slowing or reversing the progression of fibrosis [2-3]. Disitertide is primarily used to treat fibrotic diseases of various organs [4].
In LINC00941-overexpressing HCT-116 cells, Disitertide (10μM; 12h) treated cell showed increased mRNA and protein levels of ZO-1 and E-cadherin [5]. In LN229 cells, after Disitertide (100µg/mL; 10d) stimulation, SKI gene expression was significantly inhibited [6]. In MGC803 cells, Disitertide (20μM; 48h) blocks TGFβ1 signaling and effectively rescues the inhibitory effect of MFSD2A deficiency on CD8+ T cells [7].
In fibrosis rabbit mode, the macroscopic and microscopic morphology of muscles in the Disitertide (3.5mg/kg; iv; 72h) treated group was preserved, and extracellular matrix fibrosis was reduced [8].
References:
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[2]. Yang J, Zhuang Y, Liu J. Upregulation of microRNA‑590 in rheumatoid arthritis promotes apoptosis of bone cells through transforming growth factor‑β1/phosphoinositide 3‑kinase/Akt signaling[J]. International Journal of Molecular Medicine, 2019, 43(5): 2212-2220.
[3]. He W, Liang B, Wang C, et al. MSC-regulated lncRNA MACC1-AS1 promotes stemness and chemoresistance through fatty acid oxidation in gastric cancer[J]. Oncogene, 2019, 38(23): 4637-4654.
[4]. Miwa S, Yokota M, Ueyama Y, et al. Discovery of selective transforming growth factor β type II receptor inhibitors as antifibrosis agents[J]. ACS Medicinal Chemistry Letters, 2021, 12(5): 745-751.
[5]. Wu N, Jiang M, Liu H, et al. LINC00941 promotes CRC metastasis through preventing SMAD4 protein degradation and activating the TGF-β/SMAD2/3 signaling pathway[J]. Cell Death & Differentiation, 2021, 28(1): 219-232.
[6]. Kubelt C, Hellmold D, Esser D, et al. Insights into gene regulation under temozolomide-promoted cellular dormancy and its connection to stemness in human glioblastoma[J]. Cells, 2023, 12(11): 1491.
[7]. Zhang B, Wang C M, Wu H X, et al. MFSD2A potentiates gastric cancer response to anti‐PD‐1 immunotherapy by reprogramming the tumor microenvironment to activate T cell response[J]. Cancer Communications, 2023, 43(10): 1097-1116.
[8]. Cruz-Morande S, Dotor J, San-Julian M. P144 a transforming growth factor beta inhibitor peptide, generates antifibrogenic effects in a radiotherapy induced fibrosis model[J]. Current Oncology, 2022, 29(4): 2650-2661.
Disitertide (P144)是转化生长因子β1（TGF-β1）受体I型的特异性抑制剂 [1]。Disitertide与TGF-β1受体结合，阻断TGF-β1信号通路，抑制细胞外基质沉积和纤维化反应，从而减缓或逆转纤维化的进展 [2-3]。Disitertide主要用于治疗各种器官的纤维化疾病 [4]。
在LINC00941过表达的HCT-116细胞中，Disitertide（10μM; 12h）处理的细胞中ZO-1和E-钙粘蛋白的mRNA和蛋白质水平升高 [5]。在LN229细胞中，经Disitertide（100µg/mL；10d）刺激后，SKI基因表达受到显著抑制 [6]。在MGC803细胞中，Disitertide（20μM；48h）可阻断TGFβ1信号传导，并有效挽救MFSD2A缺陷对CD8+T细胞的抑制作用 [7]。
在纤维化兔模型中，Disitertide（3.5mg/kg；iv；72h）治疗组肌肉的宏观和微观形态均得以保留，细胞外基质纤维化减轻 [8]。