SIS3
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
IC50为3 μM。
SIS3是一种Smad3抑制剂。
受体相关的Smads,如Smad2和Smad3,直接与活化的TGF-受体I型相互作用。Smads与Smad4形成异聚复合体,Smad4是所有Smad途径的共同介质。
体外:在报告实验中发现,p3TP-lux的荧光素酶活性增加可以通过SIS3处理以剂量依赖性的方式消除。免疫沉淀显示,SIS3减少TGF-1诱导的Smad3磷酸化以及Smad3与Smad4的相互作用。然而,SIS3不影响Smad2的磷酸化。此外,SIS3通过降低转录活性而减弱TGF-1的作用。SIS3还可抑制TGF-1对成纤维细胞的肌成纤维细胞分化。此外,SIS3完全减少Smad3的组成型磷酸化[1]。
体内:动物研究表明,在Tie2-Cre; Loxp-EGFP小鼠中,AGEs可诱导EndoMT。免疫沉淀和蛋白印迹显示,Smad3可以被AGEs激活,但在MMECs和STZ诱导的糖尿病肾病中被SIS3抑制。此外,共聚焦显微镜和实时PCR显示,SIS3可以消除EndoMT,减少肾纤维化,以及延缓肾病进展[2]。
临床试验:到目前为止,SIS3仍处于临床前研究阶段。
参考文献:
[1] 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 Feb;69(2):597-607.
[2] Li J et al. Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy. Diabetes.2010 Oct;59(10):2612-24.
- 1. Te Zhang, Wenjie Xia, et al. "Super-enhancer hijacking LINC01977 promotes malignancy of early-stage lung adenocarcinoma addicted to the canonical TGF-β/SMAD3 pathway." J Hematol Oncol. 2022 Aug 18;15(1):114. PMID: 35982471
- 2. Hao Song, Jiaxi Song, et al. "METTL3-mediated m6A RNA methylation promotes the anti-tumour immunity of natural killer cells." Nat Commun. 2021 Sep 17;12(1):5522. PMID: 34535671
- 3. Dong Zeng, Zheng Xiao, et al. "Norcantharidin protects against renal interstitial fibrosis by suppressing TWEAK-mediated Smad3 phosphorylation." Life Sci. 2020 Nov 1;260:118488. PMID: 32979359
- 4. Yegodayev KM, Novoplansky O, et al. "TGF-Beta-Activated Cancer-Associated Fibroblasts Limit Cetuximab Efficacy in Preclinical Models of Head and Neck Cancer." Cancers (Basel). 2020;12(2):E339. PMID: 32028632
- 5. Liu W, Zhang D, et al. "TGF-β1 facilitates cell-cell communication in osteocytes via connexin43- and pannexin1-dependent gap junctions." Cell Death Discov. 2019 Oct 25;5:141. PMID: 31666990
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 489.99 |
Cas No. | 521984-48-5 |
Formula | C28H28ClN3O3 |
Solubility | ≥49 mg/mL in DMSO; insoluble in H2O; ≥11 mg/mL in EtOH with gentle warming and ultrasonic |
Chemical Name | (E)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-3-(1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one hydrochloride |
SDF | Download SDF |
Canonical SMILES | CN1C(C2=CC=CC=C2)=C(C3=C1N=CC=C3)/C([H])=C([H])/C(N4CCC5=CC(OC)=C(OC)C=C5C4)=O.Cl |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
质量控制和MSDS
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