SB431542

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.

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SB431542 Chemical Structure

SB431542 Chemical Structure
Molecular Weight: 384.39

Validation & Quality Control

Customer Reviews(9)

Quality Control & MSDS

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  • Research Area
  • Inhibition Profile
  • SB431542 Mechanism

Product Description

Biological Activity

Description 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.
Targets ALK5 [1]
IC50 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]
Features

Protocol(Only for 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.
Formulation DMSO
Dosages 1 μM solution, 100 μL/mouse
Administration Directly injected into peritoneal cavity
Solubility 1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL
* 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Callahan JF, et al. J Med Chem, 2002, 45(5), 999-1001.

[2] Inman GJ, et al. Mol Pharmacol, 2002, 62(1), 65-74.

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Chemical Information

Download SB431542 SDF
Molecular Weight (MW) 384.39
Formula

C22H16N4O3

CAS No. 301836-41-9
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms
Solubility (25°C) * In vitro DMSO 77 mg/mL (200 mM)
Water <1 mg/mL (<1 mM)
Ethanol 3 mg/mL (7 mM)
In vivo 1% DMSO/30% polyethylene glycol/1% Tween 80 30 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.
Chemical Name 4-(4-(benzo[d][1,3]dioxol-5-yl)-5-(pyridin-2-yl)-1H-imidazol-2-yl)benzamide

Research Area

Customer Reviews (9)


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Rating
Source Development 2013 140, 660-666. SB431542 purchased from Selleck
Method Proliferation Assay
Cell Lines Zebra fish cardiomyocytes
Concentrations 10 uM
Incubation Time 7 day
Results Following treatment with 10 μM CyA, 2 μM NVP AEW541 or 10 μM SB-431542, proliferation indices at 7 dpa were decreased compared with vehicle-treated controls by 30%, 53% and 64%, respectively (Fig. 3C). Similarly, proliferation indices decreased after genetic ablation by 18%, 24% and 48%, respectively (Fig. 3D). Recently, SB-431542 was shown to diminish cardiomyocyte proliferation after cryoinjury. Together, these results indicate that the Hh, Igf and Tgfβ signaling pathways are necessary for normal heart regeneration.

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Rating
Source Acta Biomater 2014 10(7):3108-16. SB431542 purchased from Selleck
Method H&E staining
Cell Lines Fibrocyte
Concentrations 100nM
Incubation Time 14 days
Results It further investigated the effects of the cytokine antagonists on the degree of implant-mediated fibrotic tissue reactions. In the long-term response it observed a reduction in the formation of the foreign body capsule with the release of SB431542 (TGF-β antagonist). The microbubble scaffold control is observed to have a capsule thickness of 213 ± 23 μM where localized treatment with SB431542 significantly reduces the capsule thickness to 119 ± 14 μM (P < 0.01).

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Rating
Source Stem Cells Dev 2013 SB431542 purchased from Selleck
Method Colony forming assay
Cell Lines iPS cells
Concentrations 2 uM
Incubation Time 18 day
Results To see if the addition of other small molecule inhibitors improves the efficacy of iPSC induction from myoblast cells in feeder-free conditions, ALK4/5/7 inhibitor SB431542 (SB), MEK inhibitor PD0325901 (PD), nonspecific GSK3 inhibitor lithium chloride (LiCl), and HDAC inhibitor VPA, all reported to enhance the efficiency of iPSC inductions, were tested in combination with NaB (Fig. 2C, D, and Supplementary Fig. S2). Addition of SB to the NaBcontaining medium enhanced the induction efficiency compared with NaB only. Further addition of PD or LiCl to the mixture did not further improve the efficiency.

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Rating
Source Stem Cells Dev 2013 SB431542 purchased from Selleck
Method Colony forming assay
Cell Lines iPS cells
Concentrations 2 uM
Incubation Time 30 day
Results To see if the addition of other small molecule inhibitors improves the efficacy of iPSC induction from myoblast cells in feeder-free conditions, ALK4/5/7 inhibitor SB431542 (SB), MEK inhibitor PD0325901 (PD), nonspecific GSK3 inhibitor lithium chloride (LiCl), and HDAC inhibitor VPA, all reported to enhance the efficiency of iPSC inductions, were tested in combination with NaB (Fig. 2C, D, and Supplementary Fig. S2). Addition of SB to the NaBcontaining medium enhanced the induction efficiency compared with NaB only. Further addition of PD or LiCl to the mixture did not further improve the efficiency.

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Rating
Source Am J Physiol Heart Circ Physiol 2012 302, H2211-H2219. SB431542 purchased from Selleck
Method Western Blot
Cell Lines vascular smooth muscle cells
Concentrations 10 uM
Incubation Time 12 h
Results To verify that Akt phosphorylation requires activation of the TGF- receptor, we preincubated SMCs for 30 min with the TGF- receptor kinase inhibitor (SB431542) and then stimulated with TGF- for 12 h. This inhibitor completely abolished TGF-induced Akt phosphorylation.

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Rating
Source Gen Comp Endocr 2012 178, 314–322. SB431542 purchased from Selleck
Method qRT-PCR
Cell Lines Granulosa cells
Concentrations 10 uM
Incubation Time 24 h
Results TGFb1 can stimulate CTGF mRNA expression in granulosa cells from both pre- and post-ovulatory follicles, and the TGFb signalling inhibitor SB431542 can completely abolish this effect.

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Rating
Source Dr. Kah-Wai Lin of Karolinska Biomics Center. SB431542 purchased from Selleck
Method Western blotting
Cell Lines MvILu cell
Concentrations 0-10 nM
Incubation Time
Results SB431542 inhibit expression of TGF-beta induced pS2 in MvILu cell.

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Rating
Source SB431542 purchased from Selleck
Method Sectional Immunohistochemistry
Cell Lines E14.5 male UGSs
Concentrations 10 μM
Incubation Time 4 d
Results Cell elongation index measured from spindle-like morphology was used to determine the effect of individual inhibitors. Prevention of MSP-induced spindle-like morphology was not observed in M-RON cells treated with wortmannin, SB203580, SP600125, Cay10512, and S31-201, suggesting that signaling from these pathways was not involved in MSP-induced EMT. A moderate effect, based on changes in elongation index, was seen when rapamycin, vismodegib, and XAV-939 were applied, suggesting that signaling from Hedgehog, Wnt /b-catenin, and FRAP/mTOR pathways played a role in MSP-induced EMT.

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Rating
Source SB431542 purchased from Selleck
Method ALP assay/Quantitative RT-PCR
Cell Lines C3H10T1/2 cells
Concentrations 10 μM
Incubation Time
Results Cotreatment with SB-431542 or SB-525334 has not only inhibited ALP activities compared with vehicle treatment but also abrogated the TAZ-mediated enhancement of ALP activities.

Product Citations (14)

Tech Support & FAQs

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