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SB431542
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
SB431542图片
CAS NO:301836-41-9
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)384.39
FormulaC22H16N4O3
CAS No.301836-41-9
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 77 mg/mL (200.3 mM)
Water: <1 mg/mL
Ethanol: 3 mg/mL (7.8 mM)
Solubility (In vivo)2% DMSO+30% PEG 300+ddH2O: 5mg/mL
SynonymsSB431542; SB-431542; SB 431542
实验参考方法
In Vitro

In vitro activity: SB 431542 inhibits the activin type I receptor ALK4 and the nodal type I receptor ALK7, which are responsible for the phosphorylation of Smad2. SB 431542 has little effect on ALK1, ALK2, ALK3, and ALK6, which show phosphorylation of Smad1. SB 431542 is a selective inhibitor of endogenous activin but has no apparent effect on BMP signaling. SB 431542 could induce both Smad2/Smad4- and Smad3/Smad4-dependent transcription. In A498 cells, SB 431542 inhibits both TGF-β1-induced collagen Iα1 and PAI-1 mRNA with IC50 of 60 nM and 50 nM, respectively. In addition, SB 431542 inhibits production of TGF-β1-induced fibronectin mRNA and protein with IC50 of 62 nM and 22 nM, respectively. SB 431542 blocks the TGF-β-mediated growth factors, including PDGF-A, FGF-2 and HB-EGF, leading to an increase in proliferation of MG63 cells. SB 431542 also inhibits TGF-β-induced c-Myc and p21 WAF1/CIP1. SB 431542 significantly suppresses TGF-β-induced G1 arrest, leading to accumulation of cells in the S phase of the cell cycle in FET, RIE, and Mv1Lu cells. SB 431542 also inhibits TGF-β-induced epithelial to mesenchymal transition (EMT) in NMuMG and PANC-1 cells. SB 431542 significantly elevates the expression of CD86 in BM-DCs and that of CD83 within CD11c+ cells suppressed by TGF-β. SB 431542 is able to induce NK activity through functional maturation and IL-12 production of human DCs.


Kinase Assay: SB 431542 is dissolved in DMSO at a concentration of 10 mM. The kinase domain of TGFβRI, from amino acid 200 to the C-terminus, and the full-length Smad3 protein are expressed as N-terminal glutathion S-transferase (GST) fusion proteins in the baculovirus expression system. Proteins are purified with glutathion Sepharose beads 4B. Basic FlashPlates are coated with 0.1 M sterile filtered sodium bicarbonate, pH 7.6, containing 700 ng of GST-Smad3 per 100 μL. Assay buffer contains 50 mM HEPES (pH 7.4), 5 mM MgCl2, 1 mM CaCl2, 1 mM DTT, 100 mM GTP, 3 μM ATP plus 0.5 μCi/well ?33P-ATP, and 85 ng of GST-ALK5 with or without SB 431542. Plates are incubated at 30 °C for 3 hours. The assay buffer is removed by aspiration, and the plate is counted on a Packard TopCount 96-well scintillation plate reader.


Cell Assay: To explore the effects of ligands, MG63 and NIH3T3 cells are seeded at a density of 8 × 104 cells/well in 6-well plates and starved (0.1% FCS for MG63 cells and 0.5% FCS for NIH3T3 cells) for 24 hours before ligand stimulation. Media containing various ligands are exchanged at 48-hours intervals. Cells are trypsinized and counted by a Coulter counter on days 2, 4, and 6 after ligand stimulation. To explore the effects of constitutively active receptors, cells are seeded at a density of 2 × 105 cells/well in 6-well plates. The next day, cells are infected with adenoviruses carrying various cDNAs at a multiplicity of infection of 100. Cells are trypsinized and counted on day 3. Cell proliferation assay is performed in the presence of 0.3 μM SB 431542.

In VivoSB 431542 triggers cytotoxic T lymphocyte (CTL) activities in the colon-26 carcinoma models and is most likely to produce antitumor immunological outcomes through alteration of DC function suppressed by TGF-β.
Animal modelBALB/c mice receive intraperitoneal (i.p.) injections of colon-26 tumor cells.
Formulation & DosageDissolved in DMSO; 1 μM solution, 100 μL/mouse; i.p. injection
References

J Med Chem. 2002 Feb 28;45(5):999-1001; Mol Pharmacol. 2002 Jul;62(1):65-74; Oncol Rep. 2010 Dec;24(6):1637-43.