SB 203580
(Synonyms: 4-(4-氟苯基)-2-(4-甲基亚磺酰基苯基)-5-(4-吡啶基)-1H-咪唑,SB 203580; RWJ 64809) 目录号 : GC13595
SB 203580是p38-MAPK（有丝分裂原活化蛋白激酶）通路的特异性抑制剂。
Cas No.:152121-47-6
Sample solution is provided at 25 µL, 10mM.
SB 203580 is a specific inhibitor of p38-MAPK (Mitogen-activated Protein Kinase) pathway [1,2]. SB 203580 inhibits p38 kinase in a manner competitive with ATP with a Ki of 21 nm [2].
SB 203580 inhibit the proliferation of human breast cancer cell line MDA-MB-231 with the IC50 value of was 85.1 µM [3]. SB 203580 inhibited IL-10 production by monocytic WEHI 274.3 cells expressing WT-p38α MAPK in a dose-dependent manner with greater than 95% inhibition at 5 µm and with an IC50 of 0.1µM [4]. IL-2-induced proliferation of primary human T cells, murine CT6 T cells, or BAF F7 B cells is prevented by the p38 MAP kinase inhibitor SB 203580 with an IC50 of 3-5µM [5].
SB-203580 demonstrated moderate to high clearance in all species tested in vivo, with non-linear elimination observed in the rat at plasma concentrations > 1000ng ml -1. Although good solution bioavailability was observed in non-rodents (78% in dog, 32% in monkey), lower and more variable bioavailability was observed in the rat and mouse (3-48%) [6]. SB 203580 treatment significantly improve the white blood cell (WBC) and platelet counts decreased significantly in the DENV-infected mice, suggesting leucopenia and thrombocytopenia, respectively [7].
References:
[1]. Barancik M, Bohacova V, Kvackajova J, Hudecova S, Krizanova O, Breier A: SB 203580, a specific inhibitor of p38-MAPK pathway, is a new reversal agent of P-glycoprotein-mediated multidrug resistance. Eur J Pharm Sci. 2001, 14: 29-36. 10.1016/S0928-0987(01)00139-7.
[2]. Peter R. Young, Megan M. McLaughlin, Sanjay Kumar, et al. Pyridinyl Imidazole Inhibitors of p38 Mitogen-activated Protein Kinase Bind in the ATP Site. The Journal of Biological Chemistry, 1997, 272(18): 12116-12121.
[3]. Duzgun SA, Yerlikaya A, Zeren S, Bayhan Z, Okur E, Boyaci I. Differential effects of p38 MAP kinase inhibitors SB 203580 and SB202190 on growth and migration of human MDA-MB-231 cancer cell line. Cytotechnology. 2017;69(4):711-24.
[4]. Guo, X., R.E. Gerl, and J.W. Schrader. 2003. Defining the involvement of p38alpha MAPK in the production of anti- and proinflammatory cytokines using an SB 203580-resistant form of the kinase. J. Biol. Chem. 278:22237-22242.
[5]. Lali, F. V., Hunt, A. E., Turner, S. J., and Foxwell, B. M. The pyridinyl imidazole inhibitor SB 203580 blocks phosphoinositide-dependent protein kinase activity, protein kinase B phosphorylation, and retinoblastoma hyperphosphorylation in interleukin-2-stimulated T cells independently of p38 mitogen-activated protein kinase. J. Biol. Chem.,275: 7395-7402,?2000
[6]. Ward KW, Prokscht JW, Azzaranot LM, et al. Preclinical pharmacokinetics of SB-203580, a potent inhibitor of p38 mitogen-activated protein kinase. Xenobiotica 2001; 31: 783-97
[7]. Sreekanth GP, Chuncharunee A, Sirimontaporn A, Panaampon J, Noisakran S, Yenchitsomanus PT, et al. SB 203580 modulates p38 MAPK signaling and Dengue virus-induced liver injury by reducing MAPKAPK2, HSP27, and ATF2 phosphorylation. PLoS One. 2016;11:e0149486.
SB 203580是p38-MAPK（有丝分裂原活化蛋白激酶）通路的特异性抑制剂。它以与ATP竞争的方式抑制p38激酶，Ki值为21纳摩尔。
SB 203580可以抑制人乳腺癌细胞系MDA-MB-231的增殖，其IC50值为85.1微米[3]。在表达WT-p38α MAPK的单核WEHI 274.3细胞中，SB 203580以剂量依赖方式抑制IL-10的产生，在5微米时可达到95%以上的抑制率，并且其IC50为0.1微米[4]。 SB 203580是p38 MAP激酶抑制剂，可以防止IL-2诱导的原代人T细胞、小鼠CT6 T细胞或BAF F7 B细胞增殖，其IC50为3-5µM [5]。
在所有测试的物种中，SB-203580在体内表现出中等到高度的清除能力，在大鼠血浆浓度>1000ng ml -1时观察到非线性消除。尽管非啮齿动物（狗78％，猴子32％）观察到良好的溶液生物利用度，但在大鼠和小鼠中观察到较低且更为不稳定的生物利用度（3-48%）[6]。 SB 203580治疗显着改善了DENV感染小鼠的白细胞计数和血小板计数明显下降，分别提示粒细胞减少和血小板减少[7]。
| Cell experiment [1]: | |
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Cell lines |
MDA-MB-231 human breast cancer cell line |
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Preparation Method |
Cells were treated at the logarithmic phase of the growth with various doses of SB 203580 (0.1, 0.5, 1, 5, 10, 25, 50, 100 µM) for 24 h |
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Reaction Conditions |
0.1, 0.5, 1, 5, 10, 25, 50, 100 µM for 24 h |
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Applications |
SB 203580 did not cause significant cytotoxicity on human MDA-MB-231 breast cancer cell line at low concentrations (0.1-10 µM) as compared to vehicle-treated (0.5% DMSO) control cells. However, the cytotoxic effects of both inhibitors were observed with higher concentrations of 25, 50 and 100 µM.. |
| Animal experiment [2]: | |
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Animal models |
Male Balb/c mice |
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Preparation Method |
Treatments with 2% DMSO alone or SB 203580 dissolved in 2% DMSO were given 1 h before and 1 h and 24 h after DENV infection intravenously. The volume of all injections was 0.4 ml. At 7 days after infection, the mice were euthanized with an overdose intraperitoneal injection of sodium pentobarbital anesthesia. |
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Dosage form |
5 mg/kg/d for 7 days, infection intravenously |
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Applications |
After the DENV-infected mice were treated with SB 203580, their liver AST levels were significantly reduced, but the changes in ALT were failed to reach statistical significance |
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References: [1]: Duzgun SA, Yerlikaya A, Zeren S, Bayhan Z, Okur E, Boyaci I. Differential effects of p38 MAP kinase inhibitors SB 203580 and SB202190 on growth and migration of human MDA-MB-231 cancer cell line. Cytotechnology. 2017;69(4):711-24. | |
| Cas No. | 152121-47-6 | SDF | |
| 别名 | 4-(4-氟苯基)-2-(4-甲基亚磺酰基苯基)-5-(4-吡啶基)-1H-咪唑,SB 203580; RWJ 64809 | ||
| 化学名 | 4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine | ||
| Canonical SMILES | CS(=O)C1=CC=C(C=C1)C2=NC(=C(N2)C3=CC=NC=C3)C4=CC=C(C=C4)F | ||
| 分子式 | C21H16FN3OS | 分子量 | 377.44 |
| 溶解度 | ≥ 18.872mg/mL in DMSO, ≥ 3.28 mg/mL in EtOH with ultrasonic | 储存条件 | Desiccate at 4°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 | 2.6494 mL | 13.2471 mL | 26.4943 mL |
| 5 mM | 0.5299 mL | 2.6494 mL | 5.2989 mL |
| 10 mM | 0.2649 mL | 1.3247 mL | 2.6494 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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