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LY364947
Cayman Chemical Item Number 13341
TGF-β RI Kinase Inhibitor; HTS 466284
(CAS 396129-53-6)
Transforming growth factor-β (TGF-β) signals through a cell surface heteromeric complex involving type I (TGF-β RI) and type II (TGF-β RII) receptors. Downstream signal transduction is mediated by the TGF-β RI kinase domain through the phosphorylation of Smad proteins. LY364947 is a selective inhibitor of TGF-β RI (TGFR-I, TβR-I, ALK-5), with an IC50 value of 59 nM.1 LY364947 less effectively inhibits TGF-β RII (IC50 = 400 nM), p38 MAPK (IC50 = 740 nM), and mixed lineage kinase-7 (MLK-7; IC50 = 1,400 nM).1,2 It inhibits TGF-β-induced cell growth (IC50 = 89 nM) in NIH 3T3 mouse fibroblasts1 and TGF-β-directed Smad phosphorylation, synthesis of fibronectin, PAI-1 and uPA protein, and matrigel invasion in MDA-MB-231 cells.3
1
Sawyer, J.S., Anderson, B.D., Beight, D.W., et al. Synthesis and activity of new aryl- and heteroaryl-substituted pyrazoleInhibitors of the transforming growth factor-b type I receptor kinase domain. J Med Chem46(19)3953-3956(2003).
2
Li, H., Wang, Y., Heap, C.R., et al. Dihydropyrrolopyrazole transforming growth factor-b type I receptor kinase domain inhibitors: A novel benzimidazole series with selectivity versus transforming growth factor-b type II receptor kinase and mixed lineage kinase-7. J Med Chem492138-2142(2006).
3
Shiou, S., Datta, P.K., Dhawan, P., et al. Smad4-dependent regulation of urokinase plasminogen activator secretion and RNA stability associated with invasiveness by autocrine and paracrine transforming growth facto. J Biol Chem281(45)33971-33981(2006).
Room temperature
in continental US; may vary elsewhere
SMILES
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C1(C2=CC=NC3=C2C=CC=C3)=CNN=C1C4=NC=CC=C4
Background Reading
Sawyer, J.S., Anderson, B.D., Beight, D.W., et al. Synthesis and activity of new aryl- and heteroaryl-substituted pyrazoleInhibitors of the transforming growth factor-b type I receptor kinase domain. J Med Chem46(19)3953-3956(2003).
Li, H., Wang, Y., Heap, C.R., et al. Dihydropyrrolopyrazole transforming growth factor-b type I receptor kinase domain inhibitors: A novel benzimidazole series with selectivity versus transforming growth factor-b type II receptor kinase and mixed lineage kinase-7. J Med Chem492138-2142(2006).
Shiou, S., Datta, P.K., Dhawan, P., et al. Smad4-dependent regulation of urokinase plasminogen activator secretion and RNA stability associated with invasiveness by autocrine and paracrine transforming growth facto. J Biol Chem281(45)33971-33981(2006).
LY364947 is available in the following screening
library: