tcsc1437 A 83-01

A 83-01 is a potent inhibitor of TGF-β type I receptor ALK5 kinase, type I activin/nodal receptor ALK4 and type I nodal receptor ALK7, with IC₅₀s of 12, 45 and 7.5 nM against the transcription induced by ALK5, ALK4 and ALK7, respectively.

IC50 & Target: IC50: 12 nM (ALK5, cell-based), 45 nM (ALK4 cell-based), 7.5 nM (ALK7 cell-based)^[1]

In Vitro: A 83-01 is a potent inhibitor of TGF-β type I receptor ALK5 kinase, type I activin/nodal receptor ALK4 and type I nodal receptor ALK7, reduces the level of ALK-5-induced transcription with an IC₅₀ of 12 nM in Mv1Lu cells, also blocks the ALK4-TD and ALK7-TD induced transcription with IC₅₀s of 45 nM and 7.5 nM in R4-2 cells, and weakly suppresses that induced by constitutively active ALK-6, ALK-2, ALK-3, and ALK-1. A 83-01 (0.03-10 µM) potently prevents the growth-inhibitory effects of TGF-β, and completely inhibits the effect at 3 µM. A 83-01 (1-10 µM) inhibits TGF-β-induced Smad activation in HaCaT cells^[1]. A 83-01 (1 µM) decreases cell motility, adhesion and invasion increased by TGF-β1 in HM-1 cells, but does not change cell proliferation^[2].

In Vivo: A 83-01 (50, 150 and 500 μg/mouse, i.p.) significantly improves survival of the mice without body weight or neurobehavioral appearances^[2]. A 83-01 (0.5 mg/kg, i.p.) shows a significantly strong antitumor effect in mice bearing M109 cells^[3].