|Inhibitor of the TGF-beta type I receptor kinase activity
......by AOBIOUS INC
|<p>SB431542 is a selective ATP-competitive inhibitor of ALK5 (activin receptor-like kinase 5) with an IC50 value of 94 nM .</p><p>SB431542 showed most potent efficacy among the series of hits screened out. It inhibited TGF-β1-induced mRNA formation in A498 cells with IC50 value of 50 nM. It also markedly reduced TGF-β-induced nuclear accumulation of Smad proteins with IC50 value of 40 nM. SB431542 was found to be a selective inhibitor for ALK4, ALK5 and ALK7, suppresses the phosphorylation of Smad2. It showed no significant inhibition of ALK1, ALK2, ALK6 and showed weak effect on ALK3 at concentration of 10 μM [1, 2].</p><p class="references">References:<br> Callahan J F, Burgess J L, Fornwald J A, et al. Identification of novel inhibitors of the transforming growth factor β1 (TGF-β1) type 1 receptor (ALK5). Journal of medicinal chemistry, 2002, 45(5): 999-1001.<br> Inman G J, Nicolás F J, Callahan J F, et al. SB-431542 is a potent and specific inhibitor of transforming growth factor-β superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Molecular pharmacology, 2002, 62(1): 65-74.<br></p>
......by Apexbio Technology LLC
|SB-431542 is potent and selective inhibitor of the transforming growth factor-β (TGF-β) type I receptor activin receptor-like kinase ALK5 (IC50 = 94 nM) and its relatives ALK4 and ALK7.
IC50 value: 94 nM 
in vitro: 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 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 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 .
in vivo: SB 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 .
Protocol(Only for Reference)
Cell Assay :
Cell line: MG63 and NIH3T3
Concentration: 0.3 uM
Method: To explore the effects of ligands, MG63 and NIH3T3 cells are seeded at a density of 8 × 10 4 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.
Animal Model Study :
Animal Model: BALB/c mice receive intraperitoneal (i.p.) injections of colon-26 tumor cells.
Dosage: 1 μM solution, 100 μL/mouse
Administration: Injected into peritoneal cavity
Solubility: 1% DMSO/30% polyethylene glycol/1% Tween 80, , 30 mg/mL
......by MedChemexpress Co., Ltd.
|SB-431542 is a novel small molecule inhibitor of the type I TGF-beta receptor, on a panel of human malignant glioma cell lines. SB-431542 blocked the phosphorylation and nuclear translocation of the SMADs, intracellular mediators of TGF-beta signaling, with decreased TGF-beta-mediated transcription. Furthermore, SB-431542 inhibited the expression of two critical effectors of TGF-beta-vascular endothelial growth factor and plasminogen activator inhibitor-1. SB-431542 treatment of glioma cultures inhibited proliferation, TGF-beta-mediated morphologic changes, and cellular motility. Together, our results suggest that small molecule inhibitors of TGF-beta receptors may offer a novel therapy for malignant gliomas by reducing cell proliferation, angiogenesis, and motility. (source: Mol Cancer Ther. 2004 Jun;3(6):737-45.) Shelf life: >2 years if stored properly Drug formulation: This drug may be formulated in DMSO
......by MedKoo Biosciences, Inc.
|SB431542 is a potent and selective inhibitor of ALK5 with IC50 of 94 nM, 100-fold more selective for ALK5 than p38 MAPK and other kinases.
......by Selleck Chemicals LLC
|SB431542 is a potent and selective inhibitor of ALK5 with IC50 of 94 nM in a cell-free assay, 100-fold more selective for ALK5 than p38 MAPK and other kinases.
......by Target Molecule Corp.