909910-43-6 Usage
Description
A-83-01, also known as 909910-43-6, is a potent and selective inhibitor of ALK4, 5, and 7 receptors, with IC50 values of 45, 12, and 7.5 nM, respectively. It prevents phosphorylation of Smad2/3 and growth inhibition induced by TGFβ. A-83-01 is cell permeable and active in vivo.
Uses
Used in Cancer Therapy:
A-83-01 is used as a selective inhibitor of TGF-β type I receptor for increasing tumor permeability, which can enhance the delivery of therapeutic agents to cancer cells and improve treatment outcomes.
Used in Drug Discovery and Development:
A-83-01 is used as an inhibitor of transforming growth factor β kinase type 1 receptor, which can help researchers understand the role of TGF-β signaling in various diseases and develop targeted therapies.
Used in Stem Cell Research:
A-83-01 is used to inhibit the differentiation of rat induced pluripotent stem cells, thereby increasing clonal expansion efficiency. This can be valuable for stem cell-based therapies and regenerative medicine.
Used in Cellular Reprogramming:
A-83-01, in combination with AMI-5, is used to enable Oct4-induced reprogramming of mouse embryonic fibroblasts. This can contribute to advancements in the field of cellular reprogramming and the development of new therapeutic approaches.
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.
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
Check Digit Verification of cas no
The CAS Registry Mumber 909910-43-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,0,9,9,1 and 0 respectively; the second part has 2 digits, 4 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 909910-43:
(8*9)+(7*0)+(6*9)+(5*9)+(4*1)+(3*0)+(2*4)+(1*3)=186
186 % 10 = 6
So 909910-43-6 is a valid CAS Registry Number.
InChI:InChI=1/C25H19N5S/c1-17-8-7-13-23(27-17)24-21(19-14-15-26-22-12-6-5-11-20(19)22)16-30(29-24)25(31)28-18-9-3-2-4-10-18/h2-16H,1H3,(H,28,31)
