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Literature summary for 2.7.11.30 extracted from

  • Zhou, L.; McMahon, C.; Bhagat, T.; Alencar, C.; Yu, Y.; Fazzari, M.; Sohal, D.; Heuck, C.; Gundabolu, K.; Ng, C.; Mo, Y.; Shen, W.; Wickrema, A.; Kong, G.; Friedman, E.; Sokol, L.; Mantzaris, I.; Mantzaris, G.; Pellagatti, A.; Boultwood, J.; Platanias, L.C.; Steidl, U.; Yan, L.; Yingling, J.M.; Lahn, M.M.
    Reduced SMAD7 leads to overactivation of TGF-beta signaling in MDS that can be reversed by a specific inhibitor of TGF-beta receptor I kinase (2011), Cancer Res., 71, 955-963.
    View publication on PubMedView publication on EuropePMC
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Application

Application Comment Organism
medicine therapeutic potential of TBRI inhibitors in myelodysplastic syndrome, MDS. The myelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by cytologic dysplasia and ineffective hematopoiesis Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
LY-2157299 LY-2157299 inhibits TGF-beta mediated SMAD2 activation and hematopoietic suppression in primary hematopoietic stem cells. In vivo administration of LY-2157299 ameliorates anemia in a TGF-beta overexpressing transgenic mouse model of bone marrow failure. Treatment with LY-2157199 stimulates hematopoiesis from primary myelodysplastic syndrome bone marrow specimens Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P36897
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-

Source Tissue

Source Tissue Comment Organism Textmining
bone marrow
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 Homo sapiens
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HS-5 cell
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 Homo sapiens
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K-562 cell
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 Homo sapiens
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Synonyms

Synonyms Comment Organism
alk5 kinase
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 Homo sapiens
TBRI
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 Homo sapiens
TBRI kinase
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 Homo sapiens
TGF-beta receptor I kinase
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 Homo sapiens

General Information

General Information Comment Organism
malfunction reduction in SMAD7 can lead to increased sensitivity to suppressive effects of TGF-beta on hematopoiesis. SMAD7, a negative regulator of TGF-beta receptor I (TBRI) kinase is markedly decreased in a large meta-analysis of gene expression studies from myelodysplastic syndrome marrow derived CD34+ cells, SMAD7 protein is also significantly decreased in myelodysplastic syndrome marrow progenitors. The increased TGF-beta signaling due to SMAD7 reduction can be effectively inhibited by TBRI (ALK5 kinase) inhibitor LY-2157299 Homo sapiens
physiological function SMAD7 is a negative regulator of TGF-beta receptor I (TBRI) kinase. The enzyme increases Smad7 via increased TGF-beta signaling Homo sapiens