SB-525334

SKU: orb1307510

Description

SB-525334 is a potent and selective inhibitor targeting the TGF-β type I receptor ALK5, with an IC50 of 14.3 nM. It is widely used in research to investigate TGF-β signaling pathways in fibrosis, cancer, and cardiovascular disease, both in cellular assays and animal models.

Research Area

Immunology & Inflammation, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 356559-20-1
• MW: 343.42
• Purity: >98%
• Formula: C₂₁H₂₁N₅
• SMILES: C(C)(C)(C)C=1NC(=C(N1)C=2N=C(C)C=CC2)C3=CC4=C(C=C3)N=CC=N4
• Target: Kinase
• Solubility: Soluble in DMSO (up tp 30 mg/ml)

Bioactivity

• Target IC50:
  ALK5:14.3 nM (cell free)|ALK4:58.5 nM
• In Vivo:
  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 . 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 .
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• In Vitro:
  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 . 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 .
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• Cell Research:
  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 .
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• Animal Research:
  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 .
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ALK4, ALK5, Inhibitor, inhibit, TβR1I, Transforming growth factor beta receptors, TGFb, TGF-b/Smad, TGFbeta/Smad, TGF-beta, TGFbeta, TGF-β Receptor, TGF-β/Smad, TGFβ, Smad, SB 525334, SB525334, SB-525334

Compound Identifiers

PubChem CID

9967941