A 83-01,909910-43-6,IC-0236813

A 83-01 is a potent inhibitor of TGF-β type I receptor ALK5 kinase, type I nodal receptor ALK4 and type I nodal receptor ALK7, with IC50 s of 12 nM,45 nM and 7.5 nM against the transcription induced by ALK5, ALK4 and ALK7, respectively [1].
A 83-01 reduces the level of ALK-5-induced transcription in Mv1Lu cells, also blocks the ALK4-TD and ALK7-TD induced transcription 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]. A-83-01-treated retinal pigment epithelium (RPE) failed to differentiate after 7 passages (P7). Exogenous expression of MYCN and OTX2 in conjunction with A 83-01 restored P7-RPE differentiation to a status similar to minimally passaged RPE [5].
When co-administrated F-SL with A 83-01. Intraperitoneally injected A 83-01-induced alterations in the cancer-associated neovasculature were examined by magnetic resonance imaging (MRI) and histological analysis. The targeting efficacy of single intravenous injections of F-SL combined with A 83-01 was evaluated by measurement of the biodistribution and the antitumor effect in mice bearing murine lung carcinoma M109. A 83-01 temporarily changed the tumor vasculature around 3 h post injection. A 83-01 induced 1.7-fold higher drug accumulation of F-SL in the tumor than liposome alone at 24 h post injection. Moreover F-SL co-administrated with A 83-01 showed significantly greater antitumor activity than F-SL alone [3]. A 83-01 treatment significantly increased the number of Nkx2.5(+) cardiomyoblasts at baseline and after myocardial injury, resulting in an increase in newly formed cardiomyocytes [6]. Using transgenic Nkx2.5 enhancer-green fluorescent protein (GFP) reporter mice, and isolated cardiac progenitor cells (CPC). A 83-01 was found to induce proliferation mainly through increasing Birc5 expression in the MEK/ERK-dependent pathway [7]. Treatment of rat dermal fibroblast with A 83-01 inhibited transforming growth factor-β1 (TGF-β1)-dependent induction of α-SMA and collagen type I [4].