SB525334

Catalog No.S1476

SB525334 Chemical Structure

Molecular Weight(MW): 343.42

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.

Size Price Stock Quantity  
In DMSO USD 64 In stock
USD 70 In stock
USD 120 In stock
USD 470 In stock
USD 870 In stock

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5 Customer Reviews

  • Increased dietary salt intake activates the Smad2 signaling pathway to promote a decrease in endothelial PTEN levels, phosphorylation of Akt at S473, and phosphorylation of NOS3 at S1177. The TβRI/ALK5 kinase inhibitor, SB525334, prevented the salt-induced increases in Smad2 phosphorylation and the downstream signaling events that included the reduction in PTEN levels and increases in phosphorylated Akt(S473) and phosphorylated NOS3(S1177). The graphs on the right represented the pertinent relative protein levels of all the animals in the study (n = 6 rats in each group). *P < 0.05 compared to the other 3 groups.

    Hypertension 2013 62(5), 951-6. SB525334 purchased from Selleck.

    LS 174T and SW480 cells were treated with SB525334 (1 umol/L) for 12 hours. HMGA2 expression was assessed by immunoblotting. Each experiment was repeated 3 times. Bars, SD; *, P < 0.05; **, P < 0.01.

    Cancer Lett 2014 355(1), 130-40. SB525334 purchased from Selleck.

  • Ang-(1-7) appears to inhibit MGA-induced fluorescent staining for de novo expression of α-SMA in NRK 52-E cells. Cells were incubated with serum free media (A and C) or MGA (100 uM, B, D-I) or TGF-β (5 ng, J) for 72 h. MGA-treated cells were treated with either Ang-(1-7) (100 nM, E), Ang-(1-7) and DAL (10 uM, F), ERK1/2 inhibitor PD98059 (1 uM, G), TGF-β receptor kinase inhibitor SB525334 (1 uM, H) or AT1 receptor antagonist losartan (1 uM, I). The immunofluorescent images are representative of 3 different cell passages.

    Cell Signal 2014 10.1016/j.cellsig.2014.09.010. SB525334 purchased from Selleck.

    The effect of ERK1/2 and Smad2/3 signaling pathway inhibition by SB525334 on the TGF-β1-stimulated expression of TIMP-3. Chondrocytes were pretreated with the TGF-β1 receptor I (ALK5) kinase inhibitor SB525334 (1 uM) for 60 min followed by stimulation with or without TGF-β1 (10 ng/ml) for 48 h. TIMP-3 protein levels, as evaluated by Western blotting.

    Cell Signal 2014 10.1016/j.cellsig.2014.09.010. SB525334 purchased from Selleck.

  •  

    (C) C3H10T1/2 cells transfected with pEF-BOS or pEF-Flag-TAZ were cultured for 8 days in osteogenic medium (OM) including ascorbic acid and β-glycerophosphate in the absence or presence of TGF-β inhibitors (SB-431542 or SB-525334). ALP activity was measured in the cell layer and normalized to cellular protein content. Data are expressed as means 6 ± SD ( *p < 0.05 vs. pEF-BOS, # p < 0.01 vs. vehicle) (D) Quantitative RT-PCR analysis of Col 1 and ALP in C3H10T1/2 cells.

    SB525334 purchased from Selleck.

Purity & Quality Control

Choose Selective TGF-beta/Smad Inhibitors

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
rhPOSTN Ml;YRZBweHSxc3nzJGF{e2G7 NH7YW5ExNjYEoN88UeKh MoPMOFjDqGh? M3qzT5Nq\26rZnnjZY51dHliZHXjdoVie2W|IITo[UBvfW2kZYKgc4Yh[XCxcITveIlkKGOnbHzz MVSyOFEzQTF6OB?=
HUVECs NFr4W|NHfW6ldHnvckBCe3OjeR?= NYewXYJKOTBizszN MXuyOE81QC95MjDo MljocIVi\HNidH:gZUBlcXO{dYD0bY9vKG:oIITo[UBJXV[HQzDtc45wdGG7ZYKgZYZ1\XJiN{KgbJI> M1TQb|I{QTZ6OUix
HUVECs NXTCOJYxTnWwY4Tpc44hSXO|YYm= MVixNEDPxE1? MUe3NkBp MUficI9kc3Nic3nncoFtcW6p NUPyOo5IOjN7Nki5PFE>
HUVECs MUDGeY5kfGmxbjDBd5NigQ>? M4POWlExKM7:TR?= NFT5fFA4OiCq MXHy[YR2[2W|IITo[UBxcG:|cHjvdplt[XSrb36gc4Yhe22jZEK= M1rQRVI{QTZ6OUix
MiaPaCa2 MmTrR4VtdCCYaXHibYxqfHliQYPzZZk> NGrqXlcxNTFyIN88US=> MknIO|IhcA>? NEOwd5Jm\m[rY3nlcpRtgSC{ZXT1Z4V{KHSqZTD2bYFjcWyrdImge4l1cCCpZX3jbZRi[mmwZR?= NHvTcZIzOjN7OUW5Oy=>
AsPC1 NIf4TlBE\WyuIG\pZYJqdGm2eTDBd5NigQ>? M1jmc|AuOTBizszN MVq3NkBp MUjl[oZq[2mnboTsfUBz\WS3Y3XzJJRp\SC4aXHibYxqfHlid3n0bEBo\W2laYThZolv\Q>? MXqyNlM6QTV7Nx?=
PASMCs  NEDMempHfW6ldHnvckBCe3OjeR?= Mn3CNUDPxE1? NFP5NVcyPSCvaX6= NH\R[mVqdmirYnn0d{BVT0ZvzsKxMY1m\GmjdHXkJJBzd2yrZnXyZZRqd25ib3[g[oFucWyrYXygbXBCUCCSQWPNR5Mh[XRiYX6gTWM2OMLib3[gNlk2KG6vb3yvUC=> NXfWcFd6OTlzMU[zOlE>
ELT-3  M{CyOmZ2dmO2aX;uJGF{e2G7 Mn\ZNE42NzFwMD:yMlAh|ryP MlO1NUBp NWPJOmNUTE2VTx?= M2P2dIlvcGmkaYTzJHRITi4QsjDzbYdv[WyrbnegbY4hdGWrb335c41iew>? M{P4eVE4PTB3MEGy

... Click to View More Cell Line Experimental Data

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

Kinase Assay
+ Expand

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 Research
+ Expand
  • 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.
    (Only for Reference)
Animal Research
+ Expand
  • Animal Models: Bleomycin-induced pulmonary fibrosis in female Eker rats
  • Formulation: 200 mg/L in drinking water
  • Dosages: Estimated dose of 10 mg/kg/day
  • Administration: Oral (in drinking water)
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 68 mg/mL (198.0 mM)
Ethanol 68 mg/mL (198.0 mM)
Water <1 mg/mL
In vivo 5% DMSO+corn oil 20mg/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.

Chemical Information

Molecular Weight 343.42
Formula

C21H21N5

CAS No. 356559-20-1
Storage powder
in solvent
Synonyms N/A

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Frequently Asked Questions

  • Question 1:

    I want to know the feasibility of using the compound via oral gavage in rodents (dosing, frequency, formulation…)?

  • Answer:

    Our S1476 can be used for oral gavage in rodents, and the vehicle we suggest is: 30% Propylene glycol, 5% Tween 80, 65% D5W (dextrose(5%)in water) at 20mg/ml maximum. Based on the following reference they administrated it at an estimated dose of 10 mg/kg/day in rat for 2 months: http://clincancerres.aacrjournals.org/content/13/10/3087.long

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID