TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000374994
  • Gene Name:TGFBR1
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:TGFβ signaling pathways
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:YR-290
  • Drug Method:down-regulated the gene expression the gene expression

Disease basic infommation

  • Disease:breast cancer
  • Tissue:cell lines (MDA-MB-231 ,Hs578T,BT-549,HaCaT)

Other information

  • Title:Inhibition of breast cancer metastases by a novel inhibitor of TGFbeta receptor 1
  • Journal:J Natl Cancer Inst
  • Published:2013
  • PubMed ID:23178439
  • Abstract:Background:Transforming growth factor beta (TGFβ), which is implicated in metastasis to various organs in breast cancer, is a potential target for new antitumor metastasis drugs. Methods:To identify specific inhibitors of TGFβ receptor 1 (TGFβR1) in breast cancer metastasis, a virtual library of more than 400000 different compounds was screened by molecular docking modeling and confirmed with Smad-binding element luciferase and TGFβR1 kinase assays. Affymetrix GeneChip expression analysis of mRNA levels and real-time polymerase chain reaction were performed to determine expression changes of TGFβ-mediated, metastasis-associated genes in breast cancer cells after treatment with the small-molecule inhibitor YR-290. YR-290 was also examined for its effects on breast cancer migration, invasion, and metastasis using transwell and epithelial-to-mesenchymal transition (EMT) assays in vitro and three different mouse (BALB/c and NU/NU nude) models (n = 10 per group). Kaplan-Meier analyses were used to assess survival. All statistical tests were two-sided. Results:YR-290 interacted with the kinase domain of TGFβR1, abrogated kinase activity (half maximal inhibitory concentration = 137nM, 95% confidence interval = 126.4 to 147.6nM) and inhibited the TGFβ-mediated downstream signaling pathway and metastasis-associated genes in breast cancer cells. YR-290 inhibited TGFβ-modulated breast cancer cell migration and invasion. In tumor metastasis mouse models, YR-290 almost completely blocked cancer metastasis. Numbers of lung tumor nodules of mice treated with 1mg/kg and 5mg/kg YR-290 were reduced by 74.93% (95% confidence interval = 61.45% to 88.41%) and 94.93% (95% confidence interval = 82.13% to 100%), respectively, compared with control mice. Treatment with YR-290 also statistically significantly prolonged the survival of tumor-bearing mice. Conclusions:YR-290 is a novel inhibitor of tumor metastasis that works by blocking TGFβ signaling pathways.
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