SB525334

製品コードS1476 バッチS147604

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C21H21N5
分子量 343.42 CAS No. 356559-20-1
Solubility (25°C)* 体外 DMSO 68 mg/mL (198.0 mM)
Ethanol 68 mg/mL (198.0 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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 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]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 Human renal proximal tubule epithelial (RPTE) cells
濃度 1 μM
反応時間 1 hour
実験の流れ

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 secondary antibody. The slides are then viewed in a confocal microscope and nuclear signal intensity is analyzed.
動物実験 動物モデル induced pulmonary fibrosis in female Eker rats
投薬量 Estimated dose of 10 mg/kg/day
投与方法 Oral (in drinking water)

参考

  • https://pubmed.ncbi.nlm.nih.gov/15769863/
  • https://pubmed.ncbi.nlm.nih.gov/19116361/
  • https://pubmed.ncbi.nlm.nih.gov/17505012/
  • https://pubmed.ncbi.nlm.nih.gov/17274978/

カスタマーフィードバック

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]

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Hybrid lipid nanoparticles with tumor antigen-primed dendritic cell membranes for post-surgical tumor immunotherapy [ J Control Release, 2025, S0168-3659(25)00029-X] PubMed: 39800239
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Enhanced THBS2 promotes collagen synthesis and inflammatory secretome of fibroblasts in idiopathic pulmonary fibrosis [ Sci Rep, 2025, 15(1):25926] PubMed: 40676074
Porphyromonas gingivalis-derived lipopolysaccharide promotes mesangial cell fibrosis via transforming growth factor-beta1/Smad signaling pathway in high glucose [ J Dent Sci, 2025, 20(2):989-994] PubMed: 40224103
Dynamic Reprogramming of Stromal Pdgfra-expressing cells during WNT-Mediated Transformation of the Intestinal Epithelium [ bioRxiv, 2025, 2025.01.22.634326] PubMed: 39896606
HDAC3 integrates TGF-β and microbial cues to program tuft cell biogenesis and diurnal rhythms in mucosal immune surveillance [ Sci Immunol, 2024, 9(99):eadk7387] PubMed: 39331726
68Ga-FAPI PET imaging monitors response to combined TGF-βR inhibition and immunotherapy in metastatic colorectal cancer [ J Clin Invest, 2024, 134(4)e170490] PubMed: 38175716
GPA33 expression in colorectal cancer can be induced by WNT inhibition and targeted by cellular therapy [ Oncogene, 2024, ] PubMed: 39472498
Cancer-associated fibroblasts barrier breaking via TGF-β blockade paved way for docetaxel micelles delivery to treat pancreatic cancer [ Int J Pharm, 2024, 665:124706] PubMed: 39277152
Brachyury promotes extracellular matrix synthesis through transcriptional regulation of Smad3 in nucleus pulposus [ Am J Physiol Cell Physiol, 2024, 326(5):C1384-C1397] PubMed: 38690917

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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