生物活性

• 描述Smads are a family of proteins with similar structure that mediates the numerous effects of the transforming growth factor beta (TGF-β) superfamily, which are critically important for tissue regeneration and homeostasis^[1]. The specific inhibitor of Smad3 (SIS3) is a synthesized chemical that specifically inhibits Smad3 with IC₅₀ value of 3 μM^[2].
  A549 cells were treated with 3 μM of SIS3 for 4h prior to 5 ng/mL TGF-β1 exposure for 48 hours. SIS3 markedly decreased the expression of p-Smad3 that was induced by TGF-β1 but did not affect total Smad3 expression as examined by western blotting assay. The results from immunofluorescence assay also indicated that the A549 cells had an obvious nuclear expression of p-Smad3 with a spindle-shaped-like morphology when treated with TGF-β1 only. However, after the pre-treatment with SIS3, the TGF-β1-induced morphological changes were not significant and the fluorescence intensity of p-Smad3 was weakened mainly in the nucleus^[3].
  In ureteral obstruction (UUO) BALB/c mouse model, 0.2 and 2 mg/kg of SIS3 was intraperitoneally injected to the mice daily for 1 week, and on the 8th post-operation day, the kidney was harvested. The phosphorylation levels of Smad3 were remarkably decreased after treating with SIS3 and the signal ligand TGF-β1 also showed suppression in a dose dependent level measured by western blotting assay^[4].
• 作用机制SIS3 can specifically inhibits Smad3 phosphorylation and its binding to Smad4 ^[4] .

• 动物研究
  剂量	UUO Mice: 0.2 mg/kg - 2 mg/kg[4] (i.p.)
  给药途径	i.p.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03686280	Stroke Sequelae	Not Applicable	Not yet recruiting	October 2021	France ... more >> Centre Mutualiste de Rééducation et Réadaptation fonctionnelles de Kerpape Not yet recruiting Ploemeur, France, 56275 Contact: Pauline Coignard, MD    0297826060 ext +33    pcoignard@kerpape.mutualite56.fr    CHU de Rennes Not yet recruiting Rennes, France, 35033 Contact: Isabelle BONAN, MD    0299289617    isabelle.bonan@chu-rennes.fr Collapse <<
  NCT01980641	Stroke	Not Applicable	Recruiting	February 2018	Spain ... more >> IBIMA Recruiting Malaga, Malaag, Spain, 29017 Contact: Antonio Cuesta-Vargas, PhD          Contact: Marina Tirado, MD          Patronato Municipal de deportes de Torremolinos Completed Torremolinos, Malaga, Spain, 29620 Collapse <<
  NCT02254343	Stroke	Not Applicable	Completed	-	Taiwan ... more >> Chang Gung Memorial Hospital Kwei-Shan, Tao-Yuan, Taiwan, 333 Lo-Sheng Sanatorium and Hospital Kwei-shan, Toayuan county, Taiwan, 333 Collapse <<

• 更多
• 参考文献

• [1] Macias MJ, Martin-Malpartida P, et al. Structural determinants of Smad function in TGF-β signaling. Trends Biochem Sci. 2015;40(6):296-308.

  [2] Jinnin M, Ihn H, 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;69(2):597-607.

  [3] Wang X, Gao JL, et al. Therapeutic effects of conditioned medium from bone marrow-derived mesenchymal stem cells on epithelial-mesenchymal transition in A549 cells. Int J Mol Med. 2018;41(2):659-668.

  [4] Ji X, Wang H, et al. Specific Inhibitor of Smad3 (SIS3) Attenuates Fibrosis, Apoptosis, and Inflammation in Unilateral Ureteral Obstruction Kidneys by Inhibition of Transforming Growth Factor β (TGF-β)/Smad3 Signaling. Med Sci Monit. 2018.