SB525334

Catalog No.S1476 Batch:S147604

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Technical Data

Formula

C21H21N5
Molecular Weight 343.42 CAS No. 356559-20-1
Solubility (25°C)* In vitro DMSO 68 mg/mL (198.0 mM)
Ethanol 68 mg/mL (198.0 mM)
Water 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.)

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Biological Activity

Description SB525334 is a potent and selective inhibitor of TGFβ receptor I (ALK5) with IC50 of 14.3 nM in a cell-free assay, 4-fold less potent to ALK4 than ALK5 and inactive to ALK2, 3, and 6.
Targets
TGFβR1(ALK5) [1]
(Cell-free assay)
14.3 nM
In vitro SB 525334 shows no inhibition in the enzymes ALK2, 3, and 6, with IC50 values > 10 μM. SB 525334 blocks phosphorylation induced by TGF-β1 and nuclear translocation of Smad2/3 in renal proximal tubule cells. SB 525334 also inhibits the increased mRNA expression levels of plasminogen activator inhibitor-1 (PAI-1) and procollagen α1(I) induced by TGF-β1 in A498 renal epithelial carcinoma cells at 1 μM). [1] SB 525334 (1 μM) attenuates the heightened sensitivity to TGF-β1 exhibited by pulmonary artery smooth muscle cells (PASMCs) from patients with familial forms of idiopathic pulmonary arterial hypertension (PAH). [2]
In vivo SB 525334 (10 mg/kg/day) decreases the renal mRNA levels of PAI-1, procollagen α1(I), and procollagen α1(III) in a nephritis-induced renal fibrosis rat model. Furthermore, PAN-induced proteinuria is significantly inhibited by SB 525334 (10 mg/kg/day). [1] SB 525334 may also be efficacious in mesenchymal tumors. SB 525334 (10 mg/kg/day) significantly decreases uterine mesenchymal tumor incidence, multiplicity, and size in Eker rats. [3] SB 525334 significantly reverses pulmonary arterial pressure and inhibits right ventricular hypertrophy in a rat model of PAH. This is revealed by a significant reduction in pulmonary arteriole muscularization induced by monocrotaline (used to induce PAH) after treatment with SB 525334 (3 or 30 mg/kg). [2] In a Bleomycin-induced pulmonary fibrosis mice model, SB 525334 (10 mg/kg or 30 mg/kg) attenuates the histopathological alterations in the lung, and significantly decreased mRNA expression of Type I and III procollagen and fibronectin. SB 525334 also attenuates Smad2/3 nuclear translocation, myofibroblast proliferation, deposition of Type I collagen, and decreases CTGF-expressing cells. [4]

Protocol (from reference)

Kinase Assay:[1]
  • Kinase assay to determine the potency and selectivity of SB 525334

    In order to determine the potency of SB 525334, purified GST-tagged kinase domain of ALK5 is incubated with purified GST-tagged full-length Smad3 in the presence of 33P-γATP and different concentrations of SB 525334. The readout is radioactively labeled Smad3. To determine the selectivity of SB 525334, purified GST-tagged kinase domain of ALK2 and ALK4 are incubated with GST-tagged full-length Smad1 and Smad3, respectively, in the presence of different concentrations of SB 525334. IC50 values are calculated.

Cell Assay:[1]
  • Cell lines

    Human renal proximal tubule epithelial (RPTE) cells

  • Concentrations

    1 μM

  • Incubation Time

    1 hour

  • Method

    RPTE cells are seeded on microscope slides. The following day, the cells are starved for 24 hours to dosing by removal of the serum and epidermal growth factor. Cells are treated with either 10 ng/mL TGF-β1, 1 μM SB 525334, or a combination of both. Slides are pretreated with SB 525334 or starve media for 3 hours prior to a 1-hour incubation at 37 °C with TGF-β1 or starve media. The cells are then fixed and permeabilized. The slides are blocked with BSA, incubated with a mouse anti-Smad2/3 primary antibody followed by an anti-mouse IgG fluorescein secondary antibody. The slides are then viewed in a confocal microscope and nuclear signal intensity is analyzed.

Animal Study:[3]
  • Animal Models

    Bleomycin-induced pulmonary fibrosis in female Eker rats

  • Dosages

    Estimated dose of 10 mg/kg/day

  • Administration

    Oral (in drinking water)

Customer Product Validation

Data from [Data independently produced by Cancer Lett, 2014, 355(1), 130-40]

Data from [Data independently produced by Cell Signal, 2014, 10.1016/j.cellsig.2014.09.010]

Data from [Data independently produced by Cell Signal, 2014, 10.1016/j.cellsig.2014.09.010]

Data from [Data independently produced by Hypertension, 2013, 62(5), 951-6]

Selleck's SB525334 has been cited by 98 publications

ESRRB Inhibits the TGFβ Signaling Pathway to Drive Cell Proliferation in Cervical Cancer [ Cancer Res, 2023, 83(18):3095-3114] PubMed: 37350664
Identification of fibrocyte cluster in tumors reveals the role in antitumor immunity by PD-L1 blockade [ Cell Rep, 2023, 42(3):112162] PubMed: 36870329
Impact of retrotransposon protein L1 ORF1p expression on oncogenic pathways in hepatocellular carcinoma: the role of cytoplasmic PIN1 upregulation [ Br J Cancer, 2023, none] PubMed: 36707636
Trichinella spiralis-Secreted Products Promote Collagen Capsule Formation through TGF-β1/Smad3 Pathway [ Int J Mol Sci, 2023, 24(19)15003] PubMed: 37834451
Glioma-derived small extracellular vesicles induce pericyte-phenotype transition of glioma stem cells under hypoxic conditions [ Cell Signal, 2023, 109:110754] PubMed: 37315748
Targeting fibrotic signaling pathways by EGCG as a therapeutic strategy for uterine fibroids [ Sci Rep, 2023, 13(1):8492] PubMed: 37231028
Mechanical force regulates Sox9 expression at the developing enthesis [ Development, 2023, 150(16)dev201141] PubMed: 37497608
The mast cell exosome-fibroblast connection: A novel pro-fibrotic pathway [ Front Med (Lausanne), 2023, 10:1139397] PubMed: 36910476
BMAL1 Promotes Valvular Interstitial Cells' Osteogenic Differentiation through NF-κ B/AKT/MAPK Pathway [ J Cardiovasc Dev Dis, 2023, 10(3)110] PubMed: 36975874
TGFB1 Induces Fetal Reprogramming and Enhances Intestinal Regeneration [ bioRxiv, 2023, 2023.01.13.523825] PubMed: 36711781

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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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