SB505124是一种选择性TGF-β I型受体（ALK4、ALK5、ALK7）抑制剂，对ALK4和ALK5的IC50值分别为129nM和47nM。
Cas No.:694433-59-5
Sample solution is provided at 25 µL, 10mM.
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SB505124 is a selective inhibitor of TGF-β Receptor type I receptors (ALK4, ALK5, ALK7), with IC50 values of 129nM and 47nM for ALK4, ALK5, respectively[1]. SB505124 can inhibit the Wnt and TGF-β1 signaling pathways, reduce inflammatory responses, and decrease the levels of fibrosis markers (such as collagen, α-SMA and fibronectin)[2]. SB505124 has been widely used to inhibit the differentiation of Th17 cells and regulate inflammation in mouse models of arthritis[3].
In vitro, SB505124 treatment at 3μM for 10 days significantly inhibited the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), reduced the formation of mineralized matrix, and downregulated osteogenic-related genes[4]. Treatment with SB505124 (2.5μM) for 24 hours significantly enhanced the sensitivity of doxorubicin (DTX)-resistant DU 145 cells to DTX and induced cell death[5]. Pretreatment of rabbit conjunctival submucosal fibroblasts with 10µM SB505124 for 1 hour significantly reduced the level of pSmad2 induced by TGF-β2 as well as the expressions of CTGF and α-SMA[6].
In vivo, SB505124 treatment via intraperitoneal injection at a dose of 10mg/kg once every 12 hours for 5 days alleviated the extent of tertiary neurodegeneration and blood-brain barrier dysfunction in the perinatal mouse model with hypoxic-ischemic brain injury, and improved sensory-motor deficits[7]. SB505124 treatment for 2 weeks (5mg/kg/day; i.p.) caused the increase of erythrocytes in the peripheral blood and the normalized proportion of erythroblast cell clusters in the Lewis lung carcinoma (LLC) cell-xenograft mouse models[8].
References:
[1] Byfield S D C, Major C, Laping N J, et al. SB-505124 is a selective inhibitor of transforming growth factor-β type I receptors ALK4, ALK5, and ALK7[J]. Molecular pharmacology, 2004, 65(3): 744-752.
[2] Tang Y, Liu J, Liu L. Angiotensin-converting Enzyme 2 Suppresses Pulmonary Fibrosis Associated with Wnt and TGF-β1 Signaling Pathways[J]. Discovery medicine, 2024, 36(190): 2274-2286.
[3] Aarts J, Van Caam A, Helsen M, et al. Ab0082 Inhibition Of Tgfβ Signaling Using Sb-505124 Blocks Th17 Differentiation And Restores The Th17/Treg Balance In Vivo, But Does Not Suppress Experimental Arthritis[J]. Annals of the Rheumatic Diseases, 2020, 79: 1341.
[4] Almuraikhi N. Inhibition of TGF‐β type I receptor by SB505124 down‐regulates osteoblast differentiation and mineralization of human mesenchymal stem cells[J]. Cell Biochemistry and Function, 2023, 41(5): 564-572.
[5] Li Y, Zhang B, Xiang L, et al. TGF-β causes docetaxel resistance in prostate cancer via the induction of Bcl-2 by acetylated KLF5 and protein stabilization[J]. Theranostics, 2020, 10(17): 7656.
[6] Sapitro J, Dunmire J J, Scott S E, et al. Suppression of transforming growth factor-β effects in rabbit subconjunctival fibroblasts by activin receptor-like kinase 5 inhibitor[J]. Molecular Vision, 2010, 16: 1880.
[7] Kanal H D, Levison S W. Neuroprotective effects of delayed TGF-β1 receptor antagonist administration on perinatal hypoxic-ischemic brain injury[J]. Developmental Neuroscience, 2024, 46(3): 188-200.
[8] Wang B, Wang Y, Chen H, et al. Inhibition of TGFβ improves hematopoietic stem cell niche and ameliorates cancer-related anemia[J]. Stem Cell Research & Therapy, 2021, 12(1): 65.
SB505124是一种选择性TGF-β I型受体（ALK4、ALK5、ALK7）抑制剂，对ALK4和ALK5的IC50值分别为129nM和47nM[1]。SB505124能够抑制Wnt和TGF-β1信号通路，减轻炎症反应，并降低纤维化标志物（如胶原蛋白、α-SMA和纤连蛋白）的水平[2]。SB505124已被广泛用于抑制Th17细胞分化，并在关节炎小鼠模型中调节炎症[3]。
在体外，使用3µM的SB505124处理10天，显著抑制了人骨髓间充质干细胞（hBMSCs）的成骨分化，减少了矿化基质的形成，并下调了成骨相关基因的表达[4]。使用2.5µM的SB505124处理24小时，显著增强了doxorubicin（DTX）耐药的DU 145细胞对DTX的敏感性，并诱导细胞死亡[5]。用10µM的SB505124预处理兔结膜黏膜下成纤维细胞1小时，显著降低了TGF-β2诱导的pSmad2水平以及CTGF和α-SMA的表达[6]。
在体内，在围产期缺氧缺血性脑损伤小鼠模型中，每隔12小时腹腔注射一次10mg/kg剂量的SB505124，持续5天，减轻了三级神经退行性病变和血脑屏障功能障碍的程度，并改善了感觉运动缺陷[7]。SB505124治疗2周（5mg/kg/day; i.p.）导致了Lewis lung carcinoma (LLC)细胞异种移植小鼠模型中外周血红细胞数量的增加，并使成红细胞簇的比例恢复正常化[8]。
| Cell experiment [1]: | |
Cell lines | Human bone marrow mesenchymal stem cells (hBMSCs) |
Preparation Method | Human bone marrow mesenchymal stem cells (hBMSCs) were cultured in Dulbecco's Modified Eagle Medium (DMEM), supplemented with 4500mg/l D-glucose, 4mM L-glutamine, 110mg/l 10% sodium pyruvate, 10% fetal bovine serum (FBS), 1% non-essential amino acids, and 1% penicillin-streptomycin. The incubator temperature was set at 37°C, humidity at 95%, and CO2 concentration at 5% to maintain cell growth. The cells were seeded in 96-well plates, with 300μl of culture medium added to each well, and 0.3, 3, and 30μM of SB505124 were added respectively. The control group cells were added with DMSO. After 72h, cell viability was analyzed. |
Reaction Conditions | 0.3, 3, and 30μM; 72h |
Applications | SB505124 treatment significantly decreased the cell viability of U87MG cells at 30μM. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | The C57BL/6 mice were raised in a standard environment and were allowed to freely consume food and water. 2×106 LLC cells were suspended in 100μl of sterile PBS, or an equal volume of PBS solution was injected subcutaneously into the left abdomen of 8-week-old male mice. From the 7th day to the 21st day after tumor implantation, 5mg/kg doses of SB505124 or DMSO were injected intraperitoneally daily. Under anesthesia, blood samples were drawn from the inferior vena cava of the mice for analysis. |
Dosage form | 5mg/kg/day for 2 weeks; i.p. |
Applications | SB505124 treatment attenuated the symptoms of cancer-related anemia in the LLC cell-xenograft mouse models. |
References: | |
| Cas No. | 694433-59-5 | SDF | |
| 化学名 | 2-[4-(1,3-benzodioxol-5-yl)-2-tert-butyl-1H-imidazol-5-yl]-6-methylpyridine | ||
| Canonical SMILES | CC1=CC=CC(=N1)C2=C(N=C(N2)C(C)(C)C)C3=CC4=C(C=C3)OCO4 | ||
| 分子式 | C20H21N3O2 | 分子量 | 335.4 |
| 溶解度 | ≥ 33.5mg/mL in DMSO | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9815 mL | 14.9076 mL | 29.8151 mL |
| 5 mM | 596.3 μL | 2.9815 mL | 5.963 mL |
| 10 mM | 298.2 μL | 1.4908 mL | 2.9815 mL |
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