CYM5442

CYM5442用途

CYM5442 是一种有效的,高选择性和口服活性的鞘氨醇 1-磷酸 (S1P1) 受体激动剂,EC50 为 1.35 nM。CYM5442 对 S1P2,S1P3,S1P4 和 S1P5 无活性。CYM5442 激活依赖 S1P1 的 p42/p44-MAPK 磷酸化。CYM5442 具有视网膜神经保护作用,并可轻松穿过中枢神经系统。

CYM5442名称

[ CAS 号 ]:
1094042-01-9

[ 英文名 ]:
CYM5442

[英文别名 ]:

CYM-5442
CYM5442

CYM5442生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> LPL受体

研究领域 >> 神经疾病

[ 靶点 ]

EC50: 1.35 nM (Sphingosine 1-phosphate (S1P1) receptor)[1]

[体外研究]

CYM5442(0.5μM；0-60分钟；HEK293细胞)处理以时间依赖的方式刺激P32正磷酸盐标记细胞中的S1P1磷酸化[1]。CYM5442在EC50为46nm的S1P1转染CHO-K1细胞中激活S1P1依赖的p42/p44 MAPK磷酸化。丙氨酸突变株R120与CYM5442(EC50为67nm)共孵育时仍能保持p42/p44 MAPK活性。CYM5442对E121A-S1P1细胞p42/p44-MAPK的激活呈浓度依赖性,平均EC50值为134nm[1]。Western Blot分析[1]细胞系：稳定表达S1P1与GFP融合的HEK293细胞,羧端浓度：0.5μM孵育时间：0分钟、2分钟、5分钟、10分钟、30分钟、60分钟。结果：刺激S1P1磷酸化呈时间依赖性。

[体内研究]

CYM5442(1 mg/kg；腹腔注射；每日；5天；成年雄性白化Wistar大鼠)治疗显示视觉诱发电位(VEP)的视觉功能保持。视网膜神经纤维层(RNFL)在CYM治疗的动物中明显较载体厚[2]。动物模型：成年雄性白化Wistar大鼠(8～10周龄,180～230g)感染眼内皮素-1(ET-1)[2]剂量：1mg/kg,腹腔注射,每日1次,连续5d,结果：视觉诱发电位(VEP)显示视觉功能保留。视网膜神经节细胞(RGCs)明显增多。

[参考文献]

[1]. Gonzalez-Cabrera PJ, et al. Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like headgroup interactions. Mol Pharmacol. 2008 Nov;74(5):1308-18.

[2]. Blanco R, et al. The S1P1 receptor-selective agonist CYM-5442 protects retinal ganglion cells in endothelin-1 induced retinal ganglion cell loss. Exp Eye Res. 2017 Nov;164:37-45.

CYM5442物理化学性质

[ 分子式 ]:
C₂₃H₂₇N₃O₄

[ 分子量 ]:
409.47800

[ 精确质量 ]:
409.20000

[ PSA ]:
89.64000

[ LogP ]:
4.16110

[ 外观性状 ]:
浅黄色固体

[ 储存条件 ]:
-20℃

CYM5442MSDS

详细MSDS(安全技术说明书)

CYM5442安全信息

[ 个人防护装备 ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ 危险品运输编码 ]:
NONH for all modes of transport

CYM5442合成路线

详细合成路线

CYM5442上下游产品

CYM5442上游产品

CYM5442下游产品

CYM5442文献

The spleen responds to intestinal manipulation but does not participate in the inflammatory response in a mouse model of postoperative ileus.

PLoS ONE 9(7) , e102211, (2014)

Postoperative ileus is characterized by a transient impairment of the gastrointestinal motility after abdominal surgery. The intestinal inflammation, triggered by handling of the intestine, is the mai...

Sphingosine-1-Phosphate/Sphingosine-1-Phosphate Receptor 2 Axis Can Promote Mouse and Human Primary Mast Cell Angiogenic Potential through Upregulation of Vascular Endothelial Growth Factor-A and Matrix Metalloproteinase-2.

Mediators Inflamm. 2016 , 1503206, (2016)

Mast cells (MC) are present in most vascularized tissues around the vasculature likely exerting immunomodulatory functions. Endowed with diverse mediators, resident MC represent first-line fine-tuners...

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