Product Details
| Product Name:
SB 525334 |
CAS No.:
356559-20-1 |
| Purity:
≥95% |
Supply Ability:
10g |
| Release date:
2024/11/17 |
Product Introduction
Bioactivity
| 名稱(chēng) | SB 525334 |
| 描述 | SB-525334 is a potent and selective inhibitor of the TGF-β1R and ALK5 (IC50: 14.3 nM). |
| 細(xì)胞實(shí)驗(yàn) | RPTE cells were seeded on microscope slides. The following day, the cells were starved by removal of epidermal growth factor and serum for 24 h prior to dosing. Cells were dosed with 10 ng/ml TGF- 1 or 1 M SB-525334 or a combination of both. Slides were pretreated with SB-525334 or starve media for 3 h prior to a 1-h incubation at 37°C with TGF- 1 or starve media. The cells were then fixed for 15 min in 4% ice-cold paraformaldehyde. The cells were permeabilized for 10 min in 0.3% Triton X-100/PBS at room temperature. The slides were incubated for 30 min in a blocking solution containing 0.3% bovine serum albumin, 10% FBS, 0.3% Triton X-100/PBS, and 5% milk in PBS. A 1:200 dilution of primary mouse anti-Smad2/3 antibody was applied to each slide for overnight incubation. A 1:200 dilution of anti-mouse IgG fluorescein secondary antibody was applied to each slide for 30 min at room temperature. The slides were then viewed using an argon blue 488 nM laser in a confocal microscope. Nuclear signal intensity was analyzed using 1D Image Analysis software. The relative intensity was determined by the mean intensity of the nucleus and expressed as percent control [1]. |
| 激酶實(shí)驗(yàn) | To determine the potency of the ALK5 inhibitor SB-525334 at the enzyme level, purified GST-tagged kinase domain of ALK5 was incubated with purified GST-tagged full-length Smad3 in the presence of 33P-γATP and different concentrations of SB525334. The readout is radioactively labeled Smad3. To determine the selectivity of SB-525334, purified GST-tagged kinase domain of ALK2 and ALK4 were incubated with GST-tagged full-length Smad1 and Smad3, respectively, in the presence of different concentrations of SB-525334 (n=3). IC50 value determinations were calculated with GraphPad software using a sigmoidal dose-response curve [1]. |
| 動(dòng)物實(shí)驗(yàn) | To identify the optimal treatment length for puromycin aminonucleoside's effect on extracellular matrix in the kidney, 18 Sprague-Dawley (SD) rats (200 –250 g) were injected with 15 mg/100 g of puromycin aminonucleoside in 0.9% saline or sham 0.9% saline only intraperitoneally. Animals were sacrificed at 24 h (n = 3+2 control), day 4 (n=3), day 8 (n = 3), day 10 (n = 3), day 15 (n = 2), and day 20 (n = 2). A 24-h urine collection and plasma sample were taken at 9:00 AM everyday. Urine and plasma chemistry were measured at GlaxoSmithKline Laboratories Animal Science using an Olympus clinical analyzer. Proteinuria was measured as a concentration (mg/deciliter) and then converted to total protein excreted over a 24-h period using urine flow (mL/24 h). The creatinine clearance was calculated by multiplying urine creatinine levels (mg/mL) by urine flow (mg/mL/100 g b.wt.) and then dividing that product by plasma creatinine (mg/mL). To determine the effect of SB-525334 on renal disease in the PAN model, SD rats were pretreated by oral gavage with 1, 3, or 10 mg/kg/day of SB-525334 once a day. The following day, PAN was injected at 15 mg/100 g to the appropriate rats. Treatment groups continued to receive SB-525334. Ten days after PAN injection the rats were sacrificed, and blood, urine, and kidneys were collected at the termination point for analysis [1]. |
| 體外活性 | SB-525334 (1 μM) blocked TGF-beta1-induced phosphorylation and nuclear translocation of Smad2/3 in renal proximal tubule cells and inhibited TGF-beta1-induced increases in plasminogen activator inhibitor-1 (PAI-1) and procollagen alpha1(I) mRNA expression in A498 renal epithelial carcinoma cells [1]. The combination with SB525334 significantly augmented the cytotoxicity of gemcitabine in both parental and gemcitabine-resistant pancreatic cancer cells. SB525334 significantly increased apoptotic cell death in gemcitabine-resistant cells [2]. |
| 體內(nèi)活性 | Orally administered doses of 1, 3, or 10 mg/kg/day SB-525334 for 11 days produced statistically significant reductions in renal PAI-1 mRNA [1]. SB-525334 (10 mg/kg or 30 mg/kg) was orally administered at twice a day. Lungs were isolated 5, 7, 9 and 14 days after Bleomycin (BLM) treatment. BLM treatment led to significant pulmonary fibrotic changes accompanied by significant upregulation of ECM mRNA expressions, Smad2/3 nuclear translocation, CTGF expression, myofibroblast proliferation and type I collagen deposition. SB-525334 treatment attenuated the histopathological alterations in the lung, and significantly decreased the type I and III procollagen and fibronectin mRNA expression [3]. |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : ＜1 mg/mL (insoluble or slightly soluble)
1eq. HCl : 34.3 mg/mL (100 mM)
|
| 關(guān)鍵字 | inhibit | Inhibitor | TGF-β Receptor | Transforming growth factor beta receptors | SB-525334 | SB 525334 |
| 相關(guān)產(chǎn)品 | Monocrotaline | SB-431542 | DMH-1 | RepSox | Crizotinib | Chromenone 1 | Ceritinib | BMP signaling agonist sb4 | Pirfenidone | A 83-01 | Galunisertib | Alantolactone |
| 相關(guān)庫(kù) | 經(jīng)典已知活性庫(kù) | 細(xì)胞因子抑制劑庫(kù) | 膜蛋白靶向化合物庫(kù) | 激酶抑制劑庫(kù) | 酪氨酸激酶分子庫(kù) | 抑制劑庫(kù) | 腫瘤免疫治療小分子化合物庫(kù) | 已知活性化合物庫(kù) | 抗癌化合物庫(kù) | TGF-β/Smad靶點(diǎn)化合物庫(kù) |
Company Profile Introduction
Target Molecule Corp. (TargetMol) is a global high-tech enterprise, headquartered in Boston, MA, specializing in chemical and biological research product and service to meet the research needs of global customers.
TargetMol has evolved into one of the biggest global compound library and small molecule suppliers and a customer based on 40+ countries. TargetMol offers over 80 types of compound libraries and a wide range of high-quality research chemicals including inhibitors, activator, natural compounds, peptides, inhibitory antibodies, and novel life-science kits, for laboratory and scientific use. Besides, virtual screening service is also available for customers who would like to conduct the computer-aided drug discovery.
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