TGF-β RI Kinase Inhibitor VIII

TGF-β RI Kinase Inhibitor VIII is a cell-permeable quinoxaline compound that acts as a potent, highly selective, ATP-competitive inhibitor against type I TGF-β receptor TβR-I/ALK5 (IC₅₀ = 14.3 nM), while exhibiting 4-fold less potency toward ALK4 (IC₅₀ = 58.5 nM) and little or no activity against ALK2/3/6 and a panel of 26 other commonly studied kinases (≤29% inhibition at 10 µM). TGF-β RI Kinase Inhibitor VIII effectively blocks (by >95%) TGF-β1-induced Smad2/3 activation (2 μM in ELT-3 cultures) and nuclear localization (1 µM in RPTE cultures), as well as TGF-β1-dependent p3TP- and ARE-luciferase transcription (0.1 μM in HaCat cultures). TGF-β RI Kinase Inhibitor VIII is an inhibitor of ACTR-IB, COL1A1(procollagen α1(I)) and PAI-1(plasminogen activator inhibitor-1).