SB431542

Catalog No.S1067 Batch:S106710

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Technical Data

Formula

C22H16N4O3
Molecular Weight 384.39 CAS No. 301836-41-9
Solubility (25°C)* In vitro DMSO 77 mg/mL (200.31 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description 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.
Targets
ALK4 [2]
(Cell-free assay)		 ALK7 [2]
(Cell-free assay)		 ALK5 [1]
(Cell-free assay)
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. [2] 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. [3] 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. [4] 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. [5] 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. [6]
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. [6]

Protocol (from reference)

Kinase Assay: [1]
  • Flashplate assay for ALK5

    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 ɤ33P-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:[4]
  • Cell lines

    MG63 and NIH3T3

  • Concentrations

    0.3 μM

  • Incubation Time

    30 minutes

  • Method

    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.

Animal Study:[6]
  • Animal Models

    BALB/c mice receive intraperitoneal (i.p.) injections of colon-26 tumor cells.

  • Dosages

    1 μM solution, 100 μL/mouse

  • Administration

    Directly injected into peritoneal cavity

Customer Product Validation

Data from [Acta Biomater, 2014, 10(7):3108-16]

Data from [Development, 2013, 140, 660-666]

Data from [Stem Cells Dev, 2013]

Data from [Stem Cells Dev, 2013]

Selleck's SB431542 has been cited by 758 publications

WNT signalling control by KDM5C during development affects cognition [ Nature, 2024, 627(8004):594-603] PubMed: 38383780
WNT signalling control by KDM5C during development affects cognition [ Nature, 2024, 10.1038/s41586-024-07067-y] PubMed: 38383780
The extracellular matrix integrates mitochondrial homeostasis [ Cell, 2024, S0092-8674(24)00638-X] PubMed: 38942015
Generation of complex bone marrow organoids from human induced pluripotent stem cells [ Nat Methods, 2024, 10.1038/s41592-024-02172-2] PubMed: 38374263
Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells [ Nat Biotechnol, 2024, 10.1038/s41587-024-02360-7] PubMed: 39223325
Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons [ Cell Stem Cell, 2024, S1934-5909(24)00094-8] PubMed: 38626772
Retinoic acid induces human gastruloids with posterior embryo-like structures [ Nat Cell Biol, 2024, 10.1038/s41556-024-01487-8] PubMed: 39164488
In vitro induction of patterned branchial arch-like aggregate from human pluripotent stem cells [ Nat Commun, 2024, 15(1):1351] PubMed: 38355589
Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously [ Nat Commun, 2024, 15(1):668] PubMed: 38253551
VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification [ Nat Commun, 2024, 15(1):583] PubMed: 38233381

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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