SRI-011381
目录号 : GC45831
SRI-011381是一种具口服活性的转化生长因子β（TGF-β）信号通路的激活剂，具有神经保护作用。
Cas No.:1629138-41-5
Sample solution is provided at 25 µL, 10mM.
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SRI-011381 is an orally active activator of the transforming growth factor β (TGF-β) signaling pathway with neuroprotective effects[1]. TGF-β is a multi-effect cytokine that regulates cell growth and differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis, and cellular immune responses[2]. SRI-011381 has important application value in the study of tissue repair and fibrotic diseases[3].
In vitro, SRI-011381 (10μM) treatment of mouse lung fibroblasts for 48h promoted cell proliferation and increased the expression of intracellular TGF-β1, neutrophil alkaline phosphatase 3 (NALP3), collagen-1, and α-smooth muscle actin (α-SMA) proteins[4].
In vivo, SRI-011381 (30mg/kg) was intraperitoneally injected into rats with heart failure (HF) model, which reversed the protective effect of SMOC2 knockdown (sh-SMOC2) against HF, aggravated cardiac injury and fibrosis, and reversed the regulation of p-Smad3, p62, LC3-II/I, and Beclin-1 by sh-SMOC2[5]. SRI-011381 (30mg/kg) was intraperitoneally injected into YAPGFAP-CKO mice with experimental autoimmune encephalomyelitis (EAE), which inhibited inflammatory infiltration, alleviated neuronal loss, and partially rescued the optic nerve and retinal defects of mice[6].
References:
[1] Wang J, Yang L, Mei J, et al. Knockdown of notch suppresses epithelial-mesenchymal transition and induces angiogenesis in oral submucous fibrosis by regulating TGF-β1[J]. Biochemical Genetics, 2024, 62(2): 1055-1069.
[2] Moustakas A, Pardali K, Gaal A, et al. Mechanisms of TGF-β signaling in regulation of cell growth and differentiation[J]. Immunology letters, 2002, 82(1-2): 85-91.
[3] Yao C, Zhou X, Weng W, et al. Aligned nanofiber nerve conduits inhibit alpha smooth muscle actin expression and collagen proliferation by suppressing TGF-β1/SMAD signaling in traumatic neuromas[J]. Experimental and Therapeutic Medicine, 2021, 22(6): 1414.
[4] Han J, Jia Y, Wang S, et al. The improvement effect of sodium ferulate on the formation of pulmonary fibrosis in silicosis mice through the neutrophil alkaline phosphatase 3 (NALP3)/transforming growth factor-β1 (TGF-β1)/α-smooth muscle actin (α-SMA) pathway[J]. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 2021, 27: e927978-1.
[5] Ren Y, Wu Y, He W, et al. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy[J]. Open Medicine, 2023, 18(1): 20230752.
[6] Wu Q, Miao X, Zhang J, et al. Astrocytic YAP protects the optic nerve and retina in an experimental autoimmune encephalomyelitis model through TGF-β signaling[J]. Theranostics, 2021, 11(17): 8480.
SRI-011381是一种具口服活性的转化生长因子β（TGF-β）信号通路的激活剂，具有神经保护作用[1]。TGF-β是一种多效的细胞因子，可调节细胞生长和分化、凋亡、细胞运动、细胞外基质的产生、血管生成和细胞免疫反应[2]。SRI-011381在组织修复、纤维化疾病研究中具有重要应用价值[3]。
在体外，SRI-011381（10μM）处理小鼠肺成纤维细胞48h，促进了细胞增殖，增加了细胞内TGF-β1、中性粒细胞碱性磷酸酶3（NALP3）、胶原蛋白-1和α-平滑肌肌动蛋白（α-SMA）蛋白的表达[4]。
在体内，SRI-011381（30mg/kg）通过腹腔注射治疗心力衰竭（HF）模型大鼠，逆转了SMOC2敲低（sh-SMOC2）对HF的保护作用，加重了心脏损伤和纤维化，逆转了sh-SMOC2对p-Smad3、p62、LC3-II/I和Beclin-1的调控[5]。SRI-011381（30mg/kg）通过腹腔注射治疗患有实验性自身免疫性脑脊髓炎（EAE）的YAPGFAP-CKO小鼠，抑制了炎症浸润，减轻了神经元丢失，部分挽救了小鼠的视神经和视网膜缺陷[6]。
| Cell experiment [1]: | |
Cell lines | Fibroblasts |
Preparation Method | Sodium ferulate (SF) solutions of different concentrations (0.04, 0.1, 0.18 and 0.28mg/mL) were prepared to treat fibroblasts for 48h. 10μM SRI-011381 solution was added to activate the TGF-β1 signaling pathway. The effect of SRI011381 on the viability of fibroblasts was detected by CCK8 assay. The effect of SRI-011381 on the expression of TGF-b1, neutrophil alkaline phosphatase 3 (NALP3), collagen-1, and alpha-smooth muscle actin (a-SMA) proteins was detected by western blot. |
Reaction Conditions | 10μM; 48h |
Applications | SRI-011381 promoted cell proliferation and increased the expression of intracellular TGF-β1, NALP3, collagen-1, and α-SMA proteins. |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley rats |
Preparation Method | To establish the rat models of Heart failure (HF), rats were adaptively fed for 1 week and fasted for 12h. The rats were intraperitoneally injected with 1.5% sodium pentobarbital (50mg/kg) for anesthesia. Then, the left coronary artery of rats was ligated at the position between the left atrial appendage and the pulmonary conus on a temperature-controlled heating pad. The abdomen was sutured in layers. Rats in the sham operation group underwent the same procedure but without the left coronary artery ligation. To further investigate the function of SMOC2 in HF development, lentivirus carrying sh-SMOC2 or short hairpin RNA negative control (sh-NC) was injected into the infarct area of HF rats immediately after induction of myocardial infarction. Therefore, rats were randomly assigned into four groups (n=6/group): sham operation (sham), HF rat model (HF), HF rat model treated with lentivirus carrying sh-NC (HF+sh-NC), and HF rat model treated with lentivirus carrying sh-SMOC2 (HF+sh-SMOC2). TGF-β agonist (SRI-011381, 30mg/kg daily) was intraperitoneally injected into rat model 5 days after lentivirus injection. After 4 weeks of injection, rats were sacrificed by cervical dislocation, and myocardial tissues were collected for subsequent assays. |
Dosage form | 30mg/kg; i.p. |
Applications | SRI-011381 reverses the protective effect of SMOC2 knockdown (sh-SMOC2) against heart failure (HF) and aggravates cardiac injury and fibrosis. SRI-011381 treatment reversed the effects of sh-SMOC2 on decreasing the levels of p-Smad3 and p62 and increasing LC3-II/I ratio and Beclin-1 levels in HF rats. |
References: | |
| Cas No. | 1629138-41-5 | SDF | |
| Canonical SMILES | O=C(NC1CCCCC1)N(CC2CCNCC2)CC3=CC=CC=C3 | ||
| 分子式 | C20H31N3O | 分子量 | 329.5 |
| 溶解度 | DMF: 15mg/mL,DMSO: 20mg/mL,Ethanol: 25mg/mL | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0349 mL | 15.1745 mL | 30.349 mL |
| 5 mM | 0.607 mL | 3.0349 mL | 6.0698 mL |
| 10 mM | 0.3035 mL | 1.5175 mL | 3.0349 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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