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| | A-83-01 Basic information |
| Product Name: | A-83-01 | | Synonyms: | A 83-01;A83-01;TGF inhibitor A-83-01;3-(6-methylpyridin-2-yl)-N-phenyl-4-(quinolin-4-yl)-1H-pyrazole-1-carbothioamide;TGF-β RI Kinase Inhibitor IV;A 83-01, >=98%;3-(6-Methyl-2-pyridinyl)-N-phenyl-4-(4-quinolinyl)-1H-pyrazole-1-carbothioamide;A-83-01AB142092);ALK5 Inhibitor IV | | CAS: | 909910-43-6 | | MF: | C25H19N5S | | MW: | 421.52 | | EINECS: | | | Product Categories: | Inhibitors;TGF-beta/Smad;Protein Kinase | | Mol File: | 909910-43-6.mol |  |
| | A-83-01 Chemical Properties |
| Melting point | 111℃ | | Boiling point | 590.0±60.0 °C(Predicted) | | density | 1.27±0.1 g/cm3(Predicted) | | storage temp. | -20°C | | solubility | DMSO: soluble5mg/mL, clear (warmed) | | pka | 8.77±0.70(Predicted) | | form | powder | | color | white to beige | | Stability: | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 2 months. |
| | A-83-01 Usage And Synthesis |
| Description | A 83-01 (909910-43-6) is a potent and selective ALK4, 5 and 7 inhibitor.1,2?IC50 = 45, 12 and 7.5 nM respectively. Prevents phosphorylation of Smad2/3 and growth inhibition induced by TGFβ.2?Inhibits differentiation of rat induced pluripotent stem cells and increases clonal expansion efficiency.3?Together with AMI-5, A83-01 enabled Oct4-induced reprogramming of mouse embryonic fibroblasts.4?Cell permeable. Active in vivo. | | Uses | A 83-01 is a selective inhibitor of TGF-β type I receptor. A 83-01 treatment increases tumor permeability. | | Uses | A 83-01 has been used as an inhibitor of transforming growth factor β kinase type 1 receptor. | | Biological Activity | Selective inhibitor of TGF- β type I receptor ALK5 kinase, type I activin/nodal receptor ALK4 and type I nodal receptor ALK7 (IC 50 values are 12, 45 and 7.5 nM respectively). Blocks phosphorylation of Smad2 and inhibits TGF- β -induced epithelial-to-mesenchymal transition. Only weakly inhibits ALK-1, -2, -3, -6 and MAPK activity. More potent than SB 431542 (4-[4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol -2-yl]benzamide). Inhibits differentiation of rat induced pluripotent stem cells (riPSCs) and increases clonal expansion efficiency. Helps maintain homogeneity and long-term in vitro self-renewal of human iPSCs. | | Biochem/physiol Actions | A 83-01 is a TGFβ kinase/activin receptor-like kinase (ALK 5) inhibitor (IC50=12 nM) that prevents phosphorylation of Smad2/3 and inhibits growth induced by TGFβ. A 83-01 blocks phosphorylation of Smad2 and inhibits TGF-β-induced epithelial-to-mesenchymal transition. Also, A 83-01 inhibits the transcriptional activity induced by TGFβ type I receptor ALK-5, activin type IB receptor ALK-4 and nodal type I receptor ALK-7. A-83-01 induces an expansion of neonatal Nkx2.5-eGFP (+) cells. | | Enzyme inhibitor | This TGFb inhibitor (FW = 421.52 g/mol; CAS 909910-43-6; Solubility: 50 mM in DMSO), named 3-(6-methyl-2-pyridinyl)-N-phenyl-4-(4-quinolinyl)-1H-pyrazole-1-carbothioamide, selectively targets TGF-β type I receptor ALK5 kinase (IC50 = 12 nM), Type I Activin/Nodal receptor ALK4 (IC50 = 45 nM), and type I nodal receptor ALK7 (IC50 = 7.5 nM), blocking the phosphorylation of Smad2 and inhibiting TGF-β-induced epithelial-to-mesenchymal transitions. TGF-β signaling inhibitors represent a useful strategy for treating patients with tumor growth and metastasis in advanced cancer. A-83-01 only weakly inhibits ALK-1, ALK-2, ALK-3, ALK-6 and MAPK. It also has little or no effect on bone morphogenetic protein type I receptors, p38 mitogen-activated protein kinase, or extracellular regulated kinase. A-83-01 inhibits Smad signaling and epithelial-to-mesenchymal transition by transforming growth factor-β. Its use also instrumental in demonstrating that attachment to Laminin-111 facilitates TGF-β-induced expression of matrix metalloproteinase-2 in synovial fibroblasts. | | storage | -20°C (protect from light) | | References | 1) Vogt. et al. (2011), The specificities of small molecule inhibitors of the TGFβ and BMP pathways; Cell Signal., 23 1831
2) Tojo et al. (2012), Characteristic differences among osteogenic cell populations of rat bone marrow stromal cells isolated from untreated, hemolyzed or Ficoll-treated marrow; Cancer Sci., 96 791
3) Li et al. (2009), Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors; Cell Stem Cell, 4 16
4) Yuan et al. (2011), Brief report: combined chemical treatment enables Oct4-induced reprogramming from mouse embryonic fibroblasts; Stem Cells, 29 549 |
| | A-83-01 Preparation Products And Raw materials |
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