SC-236

SC-236用途

SC-236 是具有口服活性的 COX-2 特异性抑制剂 (对COX-1 和COX-2 的IC50 分别为10 nM 和17.8 μM)和 PPARγ 激动剂。SC-236 可通过c-Jun 氨基端抑制激活蛋白-1 (AP-1) 活性。SC-236在小鼠模型中通过抑制ERK的磷酸化发挥抗炎作用。

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SC-236名称

[ CAS 号 ]:
170569-86-5

[ 英文名 ]:
SC-236

[英文别名 ]:

HMS3262A06
Tracazolate hydrochloride
SC236

SC-236生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 细胞凋亡 >> 细胞凋亡

研究领域 >> 癌症

研究领域 >> 心血管疾病

信号通路 >> 细胞周期/DNA损伤 >> PPAR

研究领域 >> 炎症/免疫

信号通路 >> 免疫及炎症 >> COX

[ 靶点 ]

COX-2:10 nM (IC50)

COX-1:17.8 μM (IC50)

[体外研究]

SC-236(15μM,30分钟)抑制非甾体抗炎药的副作用,并防止血管内皮细胞受到ALSS的炎症[1]。SC-236在HSCs中显著诱导PPARγ表达,并在荧光素酶报告子反式激活试验中作为有效的PPARγ激动剂[2]。SC-236以时间和浓度依赖的方式强烈抑制巨噬细胞活力[2]。SC-236单独或与15d-PGJ2联合,在培养的HSCs中诱导显著的促凋亡作用[2]。SC-236通过调节AP-1信号通路介导抗肿瘤作用[3]。westernblot分析[1]细胞系：vECs。浓度：15μM孵育时间：30min。结果：大鼠内皮细胞COX-2水平明显降低,IκBα水平明显升高,从而抑制ALSS诱导的NFκB活化和炎症反应。westernblot分析[2]细胞系：cos7细胞。浓度：3、10μM,孵育时间：18h(与15d-PGJ2合用)。结果：PPARγ激动剂具有浓度依赖性。

[体内研究]

SC-236(6 mg/kg,灌胃)在CCl4处理的动物中表现出抗纤维化特性[2]。动物模型：76只成年雄性Wistar大鼠,体重200-220g(CCl4处理)[2]。剂量：6mg/kg。给药：口服,每周3次。结果：CCl4处理后大鼠肝脏COX-2蛋白表达明显增强。显著降低肝纤维化程度。显著抑制CCl4处理大鼠α-SMA的表达。

[参考文献]

[1]. Shao-Yu Fang, et al. Reduction in MicroRNA-4488 Expression Induces NFκB Translocation in Venous Endothelial Cells Under Arterial Flow. Cardiovasc Drugs Ther. 2020 Sep 9.

[2]. Anna Planagumà, et al. The selective cyclooxygenase-2 inhibitor SC-236 reduces liver fibrosis by mechanisms involving non-parenchymal cell apoptosis and PPARgamma activation. FASEB J. 2005 Jul;19(9):1120-2.

[3]. Benjamin Chun-Yu Wong, et al. Cyclooxygenase-2 inhibitor (SC-236) suppresses activator protein-1 through c-Jun NH2-terminal kinase. Gastroenterology. 2004 Jan;126(1):136-47.

[4]. Su-Jin Kim, et al. The COX-2 inhibitor SC-236 exerts anti-inflammatory effects by suppressing phosphorylation of ERK in a murine model. Life Sci. 2007 Aug 23;81(11):863-72.

[5]. T D Penning, et al. Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide (SC-58635, celecoxib). J Med Chem. 1997 Apr 25;40(9):1347-65.

SC-236物理化学性质

[ 密度 ]:
1.5±0.1 g/cm3

[ 沸点 ]:
543.4±60.0 °C at 760 mmHg

[ 分子式 ]:
C₁₆H₁₁ClF₃N₃O₂S

[ 分子量 ]:
401.791

[ 闪点 ]:
282.4±32.9 °C

[ 精确质量 ]:
401.021271

[ PSA ]:
86.36000

[ LogP ]:
4.32

[ 蒸汽压 ]:
0.0±1.5 mmHg at 25°C

[ 折射率 ]:
1.625

SC-236安全信息

[ 符号 ]:

GHS06

[ 信号词 ]:
Danger

[ 危害声明 ]:
H301

[ 警示性声明 ]:
P301 + P310

[ 危险品运输编码 ]:
UN 2811 6.1 / PGIII

[ 海关编码 ]:
2935009090

SC-236海关

[ 海关编码 ]: 2935009090

[ 中文概述 ]:
2935009090 其他磺（酰）胺. 增值税率:17.0% 退税率:9.0% 监管条件:无最惠国关税:6.5% 普通关税:35.0%

[ 申报要素 ]: 品名, 成分含量, 用途

[ Summary ]:
2935009090 other sulphonamides VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:35.0%

SC-236文献

Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration.

Biol. Chem. 396 , 803-12, (2015)

Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors re...

Inhibition of COX-1 attenuates the formation of thromboxane A2 and ameliorates the acute decrease in glomerular filtration rate in endotoxemic mice.

Am. J. Physiol. Renal Physiol. 309 , F332-40, (2015)

Thromboxane (Tx) A2 has been suggested to be involved in the development of sepsis-induced acute kidney injury (AKI). Therefore, we investigated the impact of cyclooxygenase (COX)-1 and COX-2 activity...

COX-2 gene dosage-dependent defects in kidney development.

Am. J. Physiol. Renal Physiol. 310 , F1113-22, (2016)

Deletion of cyclooxygenase (COX)-2 causes impairment of kidney development, including hypothrophic glomeruli and cortical thinning. A critical role for COX-2 is seen 4-8 days postnatally. The present ...

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