| CAS |
No.129-56-6 |
| 中文名称 |
吡唑蒽酮(10mM in DMSO,无菌） |
| 英文名称 |
SP600125(10mM in DMSO，Sterile） |
| 分子式 |
C14H8N2O |
| 分子量 |
220.23 |
| 溶解性 |
请根据自己的实验要求使用。 |
| 外观(性状) |
无菌溶液 |
| 储存条件 |
Stroe at -20℃，6 months. |
| 靶点 |
Ferroptosis;JNK |
| 通路 |
Apoptosis;MAPK |
| 背景说明 |
是一种有效的，可逆的，ATP竞争性的 JNK 抑制剂，也是一种有效的铁死亡 (ferroptosis) 抑制剂。 |
| 生物活性 |
SP600125 is an orally active， reversible， and ATP-competitive JNK inhibitor with IC50s of 40， 40 and 90 nM for JNK1， JNK2 and JNK3， respectively. SP600125 is a potent ferroptosis inhibitor. SP600125 induces the transformation of bladder cancer cells from autophagy to apoptosis.[1-6] |
| In Vitro |
SP600125 是 JNK2 的 ATP 竞争性抑制剂，Ki 值为 0.19±0.06 μM。SP600125 在 Jurkat T 细胞中抑制 c-Jun 的磷酸化，IC50 为 5 μM 至 10 μM。在 CD4+ 细胞中，例如从人脐带血或外周血中分离的 Th0 细胞，SP600125 阻断细胞活化和分化并抑制炎症基因 COX-2、IL-2、IL-10、IFN-γ 和 TNF-α，IC50 为 5 μM 至 12 μM[1]。 在小鼠 β 细胞 MIN6 中，SP600125 (20 μM) 诱导 p38 MAPK 的磷酸化及其下游 CREB 依赖性启动子激活[2]。 在 HCT116 细胞中，SP600125 (20 μM) 阻断 G2 期到有丝分裂的转变并诱导核内复制。SP600125 的这种能力独立于 JNK 抑制，但由于其抑制 Aurora A 和 Polo 样激酶 1 上游的 CDK1-细胞周期蛋白 B 激活[3]。 |
| In Vivo |
SP600125 (15 mg/kg 或 30 mg/kg；静脉注射) 显著抑制 TNF-α 血清水平，而 30 mg/kg 口服施用后，则剂量依赖性地阻断 TNF-α 表达[1]。 SP600125 在大鼠体内减轻 LPS 诱导的 ALI。SP600125 组大鼠 BALF 中 TNF-α和 IL-6 的表达水平显著降低[4]。 |
| 细胞实验 |
Determination of mRNA half-life is performed essentially， except that CD14+ cells are stimulated with (bacterial) lipopolysaccharide (LPS; 50 ng/mL) for 2 h before addition of actinomycin D (5 μg/mL). SP600125 (25 μM) or vehicle (0.5% DMSO vol/vol) is added immediately following the actinomycin D. Analysis is performed by using real-time reverse transcription (RT)-PCR. Total RNA is extracted with an RNeasy Mini kit. TNF mRNA is measured by real time RT-PCR， using a TNF Taqman probe. All data are normalized by using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression. The TNF-α forward primer is 5′-CTGGCCCAGGCAGTCAGAT-3′ and the reverse primer is 5′-TATCTCTCAGCTCCACGCCATT-3′. The Taqman probe sequence is 5′-FAM-CCTGTAGCCCATGTTGTAGCAAACCCTCA-TAMRA-3′[1]. |
| 动物实验 |
Mice[1] Female CD-1 mice (8-10 weeks of age) are dosed i.v. or per oswith SP600125 in PPCES vehicle (30% PEG-400/20% polypropylene glycol/15% Cremophor EL/5% ethanol/30% saline)， final volume of 5 mL/kg， 15 min before i.v. injection with LPS in saline (0.5 mg/kg). At 90 min， a terminal bleed is obtained from the abdominal vena cava， and the serum is recovered. Samples are analyzed for mouse TNF-α by using an ELISA. Rats[4] A total of 40 male Wistar rats are randomly divided into four groups (n=10): the control group， LPS group， normal saline group (NS) and the SP600125 group. Acute lung injury (ALI) is induced via intratracheal injection of LPS. Normal saline or SP600125 is administered via intraperitoneal injection (15 mg/kg) 10 min after the LPS injection. |
| 数据来源文献 |
[1]. Bennett BL， et al. SP600125， an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci U S A， 2001， 98(24)， 13681-13686.
[2]. Vaishnav D， et al. SP600125， an inhibitor of c-jun N-terminal kinase， activates CREB by a p38 MAPK-mediated pathway. Biochem Biophys Res Commun， 2003， 307(4)， 855-860.
[3]. Kim JA， et al. SP600125 suppresses Cdk1 and induces endoreplication directly from G2 phase， independent of JNK inhibition. Oncogene， 2010， 29(11)， 1702-1716.
[4]. Zheng Y， et al. JNK inhibitor SP600125 protects against lipopolysaccharide-induced acute lung injury via upregulation ofclaudin-4. Exp Ther Med. 2014 Jul;8(1):153-158.
[5]. Zhang H， et al. SP600125 Suppresses Keap1 Expression and Results in NRF2-mediated Prevention of Diabetic Nephropathy. J Mol Endocrinol. J Mol Endocrinol. 2018 Feb;60(2):145-157.
[6]. Yatsushige H， et al. Role of c-Jun N-terminal kinase in cerebral vasospasm after experimental subarachnoid hemorrhage. Stroke. 2005 Jul;36(7):1538-43. |
| 规格 |
1ml |
| 单位 |
瓶 |
中文
英语
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