SB-431542 (hydrate)
目录号 : GC48070
Inhibitor of receptors ALK4, ALK5, and ALK7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
SB-431542 is a potent and selective inhibitor of the TGF-
1.Callahan, J.F., Burgess, J.L., Fornwald, J.A., et al.Identification of novel inhibitors of the transforming growth factor ß1 (TGF-ß1) type 1 receptor (ALK5)Journal of Medicinal Chemistry45(5)999-1001(2002) 2.Laping, N.J., Grygielko, E., Mathur, A., et al.Inhibition of Transforming Growth Factor (TGF)-ß1-Induced Extracellular Matrix with a Novel Inhibitor of the TGF-ß Type I Receptor Kinase Activity: SB-431542Molecular Pharmacology62(1)58-64(2002) 3.Inman, G.J., NicolÁs, F.J., Callahan, J.F., et al.SB-431542 is a potent and specific inhibitor of transforming growth factor-β superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7Molecular Pharmacology62(1)65-74(2002) 4.James, D., Levine, A.J., Besser, D., et al.TGFß/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cellsDevelopment1321273-1282(2005) 5.Chambers, S.M., Fasano, C.A., Papapetrou, E.P., et al.Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signalingNature Biotechnology27(3)275-280(2009)
| Cas No. | N/A | SDF | |
| Canonical SMILES | NC(C(C=C1)=CC=C1C2=NC(C3=CC=C(OCO4)C4=C3)=C(C5=CC=CC=N5)N2)=O.O | ||
| 分子式 | C22H16N4O3.XH2O | 分子量 | 384.4 |
| 溶解度 | DMF: 20 mg/ml,DMSO: 20 mg/ml,DMSO:PBS(pH7.2) (1:1): 0.5 mg/ml,Ethanol: 2 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6015 mL | 13.0073 mL | 26.0146 mL |
| 5 mM | 0.5203 mL | 2.6015 mL | 5.2029 mL |
| 10 mM | 0.2601 mL | 1.3007 mL | 2.6015 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Nrf2 protects stellate cells from Smad-dependent cell activation
PLoS One 2018 Jul 20;13(7):e0201044.PMID:30028880DOI:10.1371/journal.pone.0201044.
Hepatic stellate cells (HSC) orchestrate the deposition of extracellular matrix (ECM) and are the primary effector of liver fibrosis. Several factors, including TGF-β1, PDGF and oxidative stress, have been shown to trigger HSC activation. However, the involvement of cellular defence mechanisms, such as the activation of antioxidant response by Nrf2/Keap1 in the modulation of HSC activation is not known. The aim of this work was to elucidate the role of Nrf2 pathway in HSC trans-differentiation involved in the development of fibrosis. To this end, we repressed Nrf2 and Keap1 expression in HSC with specific siRNAs. We then assessed activation markers, as well as proliferation and migration, in both primary and immortalised human HSCs exposed to Smad inhibitors (SB-431542 hydrate and SB-525334), TGF-β1 and/or PDGF. Our results indicate that knocking down Nrf2 induces HSC activation, as shown by an increase in αSMA-positive cells and by gene expression induction of ECM components (collagens and fibronectin). HSC with reduced Nrf2-levels also showed an increase in migration and a decrease in proliferation. We could also demonstrate that the activation of Nrf2-deficient HSC involves the TGF-β1/Smad pathway, as the activation was successfully inhibited with the two tested Smad inhibitors. Moreover, TGF-β1 elicited a stronger induction of HSC activation markers in Nrf2 deficient cells than in wild type cells. Thus, our data suggest that Nrf2 limits HSCs activation, through the inhibition of the TGF-β1/Smad pathway in HSCs.
Transforming growth factor beta 1 increases collagen content, and stimulates procollagen I and tissue inhibitor of metalloproteinase-1 production of dental pulp cells: Role of MEK/ERK and activin receptor-like kinase-5/Smad signaling
J Formos Med Assoc 2017 May;116(5):351-358.PMID:27720345DOI:10.1016/j.jfma.2016.07.014.
Background/purpose: In order to clarify the role of transforming growth factor beta 1 (TGF-β1) in pulp repair/regeneration responses, we investigated the differential signaling pathways responsible for the effects of TGF-β1 on collagen turnover, matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of metalloproteinase-1 (TIMP-1) production in human dental pulp cells. Methods: Pulp cells were exposed to TGF-β1 with/without pretreatment and coincubation by 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenyl mercapto)butadiene (U0126; a mitogen-activated protein kinase kinase [MEK]/extracellular signal-regulated kinase [ERK] inhibitor) and 4-(5-benzol[1,3]dioxol-5-yl-4-pyrldin-2-yl-1H- imidazol-2-yl)-benzamide hydrate (SB431542; an activin receptor-like kinase-5/Smad signaling inhibitor). Sircol collagen assay was used to measure cellular collagen content. Culture medium procollagen I, TIMP-1, and MMP-3 levels were determined by enzyme-linked immunosorbent assay. Results: TGF-β1 increased the collagen content, procollagen I, and TIMP-1 production, but slightly decreased MMP-3 production of pulp cells. SB431542 and U0126 prevented the TGF-β1-induced increase of collagen content and TIMP-1 production of dental pulp cells. Conclusion: These results indicate that TGF-β1 may be involved in the healing/regeneration processes of dental pulp in response to injury by stimulation of collagen and TIMP-1 production. These events are associated with activin receptor-like kinase-5/Smad2/3 and MEK/ERK signaling.
Identification of small molecular compounds and fabrication of its aqueous solution by laser-ablation, expanding primordial cartilage
Osteoarthritis Cartilage 2011 Feb;19(2):233-41.PMID:21094690DOI:10.1016/j.joca.2010.11.007.
Objective: The discovery of small molecular compounds that expand cartilage is needed. We searched for small molecular compounds that expand cartilage or enhance the actions of bone morphogenetic proteins (BMPs) on cartilage. Design: Metatarsal primordial cartilage explants prepared from 14.5 days postcoitum (d.p.c.) mouse embryos were organ-cultured in the presence or absence of BMPs and/or 4-(5-Benzol[1,3]dioxol-5-yl-4-pyrldin-2-yl-1H-imidazol-2-yl)-benzamide hydrate (BPIB) and its related molecules. The perichondrium was removed from some of the cartilage explants by partial digestion with collagenase. BPIB aqueous solution was prepared by fragmenting BPIB crystals in water with laser irradiation and then added to cartilage explants in organ culture. Results: We found that small molecular compounds, BPIB, available as SB431542 from Sigma and its related molecules, expand primordial cartilage explants in organ culture. These molecules are transforming growth factor-β (TGF-β) inhibitors, and the addition of excess TGF-β reduced cartilage expansion induced by these molecules. The co-administration of BPIB and BMPs synergistically expanded cartilage explants. Removal of the perichondrium abolished BIPB-induced cartilage expansion but not BMP-induced cartilage-expansion, suggesting that BPIB, but not BMPs, expands cartilage through the perichondrium. Furthermore, we used the laser-ablation technique to generate BPIB aqueous solution in the presence of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) without the use of hazardous dimethyl sulfoxide (DMSO). The laser-ablation-generated BPIB aqueous solution was more stable, expanded cartilage explants more effectively than BPIB colloidal solution prepared with DMSO, and synergistically enhanced BMP-induced cartilage expansion. Conclusions: A small molecular compound, BPIB, expands primordial cartilage explants. A BPIB aqueous solution was created by laser-ablation without using DMSO and proved to be biologically active.
Transforming growth factor β1 down-regulates Runx-2 and alkaline phosphatase activity of human dental pulp cells via ALK5/Smad2/3 signaling
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011 Mar;111(3):394-400.PMID:21236710DOI:10.1016/j.tripleo.2010.09.079.
Objective: Transforming growth factor β1 (TGF-β1) plays a role in repair and dentinogenesis in dental pulp. The purpose of this study was to study how TGF-β1 affects 2 differentiation markers, Runt-related transcription factor 2 (Runx-2) and ALP, in dental pulp cells. Study design: Primary-cultured human dental pulp cells were treated with TGF-β1 with or without pretreatment and coincubation with 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene (U0126, a mitogen-induced extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor), Noggin (a bone morphogenetic protein inhibitor), or 4-(5-benzol[1,3]dioxol-5-yl-4-pyrldin-2-yl-1H-imidazol-2-yl)-benzamide hydrate (SB431542, an activin receptor-like kinase (ALK) 5/Smad2/3 inhibitor). The differentiation status of pulp cells was evaluated by ALP staining and quantitative ALP activity assay. Changes in ALP and Runx-2 mRNA expression were determined by reverse-transcription polymerase chain reaction. Results: Cells under the treatment of TGF-β1 (5 and 10 ng/mL) showed a decrease in ALP activity and gene expression of ALP and Runx-2. Pretreatment by U0126 and Noggin was not effective to prevent the TGF-β1-induced decline of ALP activity. Interestingly, SB431542 prevented the TGF-β1-induced decline of ALP activity and ALP and Runx-2 gene expression. Conclusion: TGF-β1 down-regulates Runx-2 and ALP in human dental pulp cells via ALK5/Smad2/3 signaling. These events may play important roles at specific stages of pulpal repair and dentinogenesis.