SKF-86002
(Synonyms: 6-(4-氟苯基)-5-(4-吡啶基)-2,3-二氢咪唑并[2,1-B]-噻唑) 目录号 : GC37646
An anti-inflammatory agent
Cas No.:72873-74-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
SKF 86002 is an anti-inflammatory agent.1,2,3,4 It inhibits rat seminal vesicle prostaglandin H2 (PGH2) synthase (IC50 = 120 ?M), as well as prostanoid production by rat basophilic leukemia (RBL-1) cells and human monocytes (IC50s = 70 and 1 ?M, respectively).1 SKF 86002 inhibits leukotriene B4 (LTB4) and LTC4 production induced by A23187 in human neutrophils and monocytes, respectively (IC50 = 20 ?M for both). It also inhibits LPS-induced IL-1 production in human monocytes (IC50 = 1.3 ?M).2 SKF 86002 (10, 30, and 90 mg/kg) reduces hindleg volume in rat models of adjuvant- or collagen-induced arthritis.3 It also decreases serum levels of TNF-α and increases survival in a mouse model of LPS and galactosamine-induced endotoxic shock when administered at a dose of 100 mg/kg.4
1.Griswold, D.E., Marshall, P.J., Webb, E.F., et al.SK&F 86002: A structurally novel anti-inflammatory agent that inhibits lipoxygenase- and cyclooxygenase-mediated metabolism of arachidonic acidBiochem. Pharmacol.36(20)3463-3470(1987) 2.Lee, J.C., Griswold, D.E., Votta, B., et al.Inhibition of monocyte IL-1 production by the anti-inflammatory compound, SK&F 86002Int. J. Immunopharmacol.10(7)835-843(1988) 3.DiMartino, M.J., Griswold, D.E., Berkowitz, B.A., et al.Pharmacologic characterization of the antiinflammatory properties of a new dual inhibitor of lipoxygenase and cyclooxygenaseAgents Actions20(1-2)113-123(1987) 4.Badger, A.M., Olivera, D., Talmadge, J.E., et al.Protective effect of SK&F 86002, a novel dual inhibitor of arachidonic acid metabolism, in murine models of endotoxin shock: Inhibition of tumor necrosis factor as a possible mechanism of actionCirc. Shock27(1)51-61(1989)
| Cas No. | 72873-74-6 | SDF | |
| 别名 | 6-(4-氟苯基)-5-(4-吡啶基)-2,3-二氢咪唑并[2,1-B]-噻唑 | ||
| Canonical SMILES | FC1=CC=C(C2=C(C3=CC=NC=C3)N4C(SCC4)=N2)C=C1 | ||
| 分子式 | C16H12FN3S | 分子量 | 297.35 |
| 溶解度 | DMSO: 33.33 mg/mL (112.09 mM) | 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 | 3.363 mL | 16.8152 mL | 33.6304 mL |
| 5 mM | 0.6726 mL | 3.363 mL | 6.7261 mL |
| 10 mM | 0.3363 mL | 1.6815 mL | 3.363 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。
p38 MAP kinase inhibition ameliorates cisplatin nephrotoxicity in mice
Am J Physiol Renal Physiol 2005 Jul;289(1):F166-74.PMID:15701814DOI:10.1152/ajprenal.00401.2004.
Cisplatin is an important chemotherapeutic agent but can cause acute renal injury. Part of this acute renal injury is mediated through tumor necrosis factor-alpha (TNF-alpha). The pathway through which cisplatin mediates the production of TNF-alpha and injury is not known. Cisplatin activates p38 MAPK and induces apoptosis in cancer cells. p38 MAPK activation leads to increased production of TNF-alpha in ischemic injury and in macrophages. However, little is known concerning the role of p38 MAPK in cisplatin-induced renal injury. Therefore, we examined the effect of cisplatin on p38 MAPK activity and the role of p38 MAPK in mediating cisplatin-induced TNF-alpha production and renal injury. In vitro, cisplatin caused a dose-dependent activation of p38 MAPK in proximal tubule cells. Inhibition of p38 MAPK activation led to inhibition of TNF-alpha production. In vivo, mice treated with a single dose of cisplatin (20 mg/kg body wt) developed severe renal dysfunction at 72 h [blood urea nitrogen (BUN): 154 +/- 34 mg/dl, creatinine: 1.4 +/- 0.4 mg/dl], which was accompanied by an increase in kidney p38 MAPK activity and an increase in infiltrating leukocytes. However, animals treated with the p38 MAPK inhibitor SKF-86002 along with cisplatin showed less renal dysfunction (BUN: 55 +/- 14 mg/dl, creatinine: 0.3 +/- 0.02 mg/dl, P < 0.05), less severe histological damage, and fewer leukocytes compared with cisplatin+vehicle-treated animals. Serum levels of TNF-alpha, sTNFRI, and sTNFRII also increased significantly in cisplatin-treated mice compared with SKF-86002-treated mice (P < 0.05). Kidney mRNA levels of TNF-alpha were significantly increased in cisplatin-treated mice compared with either SKF-86002- or saline-treated animals. The hydroxyl radical scavenger DMTU (100 mg.kg body wt(-1).day(-1)) prevented the activation of p38 MAPK by cisplatin both in vitro and in vivo. DMTU also completely prevented cisplatin-induced renal injury (BUN: 140 +/- 27 vs. 22 +/- 2 mg/dl, P < 0.005) and the increase in serum TNF-alpha (33 +/- 7 vs. 4 +/- 2 pg/ml, P < 0.005) and kidney TNF-alpha mRNA in vivo. We conclude that hydroxyl radicals, either directly or indirectly, activate p38 MAPK and that p38 MAPK plays an important role in mediating cisplatin-induced acute renal injury and inflammation, perhaps through production of TNF-alpha.
p38 Kinase is a negative regulator of angiotensin II signal transduction in vascular smooth muscle cells: effects on Na+/H+ exchange and ERK1/2
Circ Res 1998 Oct 19;83(8):824-31.PMID:9776729DOI:10.1161/01.res.83.8.824.
Activation of the Na+/H+ exchanger isoform-1 (NHE-1) by angiotensin II is an early signal transduction event that may regulate vascular smooth muscle cell (VSMC) growth and migration. Many signal transduction events stimulated by angiotensin II are mediated by the mitogen-activated protein (MAP) kinases. To define their roles in angiotensin II-mediated NHE-1 activity, VSMCs were treated with angiotensin II and the activities of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases 1 and 2 (ERK1/2) were measured. Angiotensin II rapidly (peak, 5 minutes) activated p38 and ERK1/2, whereas JNK was activated more slowly (peak, 30 minutes). Because angiotensin II stimulated Na+/H+ exchange within 5 minutes, the effects of p38 and ERK1/2 antagonists on Na+/H+ exchange were studied. The MEK-1 inhibitor PD98059 decreased ERK1/2 activity and Na+/H+ exchange stimulated by angiotensin II. In contrast, the specific p38 antagonist SKF-86002 increased Na+/H+ exchange. Two mechanisms were identified that may mediate the effects of p38 and SKF-86002 on angiotensin II-stimulated Na+/H+ exchange. First, angiotensin II activation of ERK1/2 was increased 1. 5- to 2.5-fold (depending on assay technique) in the presence of SKF-86002, demonstrating that p38 negatively regulates ERK1/2. Second, the ability of angiotensin II-stimulated MAP kinases to phosphorylate a glutathione S-transferase fusion protein containing amino acids 625 to 747 of NHE-1 in vitro was analyzed. The relative activities of endogenous immunoprecipitated p38, ERK1/2, and JNK were 1.0, 2.0, and 0.05 versus control, respectively suggesting that p38 and ERK1/2, but not JNK, may phosphorylate NHE-1 in VSMC. These data indicate important roles for p38 and ERK1/2 in angiotensin II-mediated regulation of the Na+/H+ exchanger in VSMC.