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A 83-01 is a selective inhibitor of TGF-beta type I receptor ALK5 kinase, type I activin/nodal receptor ALK4 and type I nodal receptor ALK7 (IC50 values are 12, 45 and 7.5 nM respectively). IC50 Value: 12 nM ( ALK5) Target: ALK5 A 83-01 blocks phosphorylation of Smad2 and inhibits TGF-beta-induced epithelial-to-mesenchymal transition. A 83-01 only weakly inhibits ALK-1, -2, -3, -6 and MAPK activity and is more potent than SB 431542. in vitro: A-83-01, an inhibitor of TGF-beta type I receptor, increased the expression of Myf5 and MyoD, and enhanced myotube formation [1]. Microarray analysis of HM-1 cells treated with TGF-beta1 and/or A-83-01 revealed that A-83-01 efficiently inhibited transcriptional changes that are induced by TGF-beta1 [2]. -83-01 treatment significantly increased these parameters within 24 h that was positively related to pericyte coverage and tumor cell proliferation. Furthermore, apparent diffusion coefficient (ADC) determined by diffusion-weighed imaging was decreased by A-83-01 treatment, suggesting the decrease of tumor interstitial fluid pressure. Vascular function of the tumor improved by A-83-01treatment well assessed on post-Gd-L-enhanced MR images [3]. in vivo: 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 [4].
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