The transforming growth factor-β (TGF-β) type I receptor kinase ALK5 (activin receptor-like kinase 5) is an attractive target for intervention in TGFβ signaling due to its druggability as well as its centrality and specificity in the pathway[1]. TP0427736 potently inhibited ALK5 activity, with an IC50 value of 2.72 nM. Its ability to inhibit ALK3 was quite low compared with ALK5, with an IC50 value of 836 nM.[2]. TP0427736 inhibits Smad2/3 phosphorylation in A549 cells induced by TGF-β1 in a concentration-dependent manner, with an IC50 value of 8.68 nM. TP0427736 rescues proliferation of outer root sheath cells suppressed by TGF-β[2]. The topical application of TP0427736 significantly decreased Smad2 phosphorylation in mouse skin, and its repeated application suppressed the shortening of average hair follicle length during the transition from the late anagen phase to the catagen phase[2]
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