LY-294,002 盐酸盐

LY-294,002 盐酸盐用途

LY294002盐酸盐是一种有效的广谱PI3K抑制剂,P110α、P110δ和P110β的IC50值分别为0.5、0.57和0.97μM。LY294002盐酸盐也抑制CK2,IC50为98 nM。LY294002盐酸盐可用于胰腺癌研究[1][2][3]。

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LY-294,002 盐酸盐名称

[ CAS 号 ]:
934389-88-5

[ 中文名 ]:
LY-294,002 盐酸盐

[ 英文名 ]:
LY-294,002 hydrochloride

[英文别名 ]:

LY-294,002 hydrochloride

LY-294,002 盐酸盐生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 细胞凋亡 >> 细胞凋亡

研究领域 >> 癌症

信号通路 >> 细胞周期/DNA损伤 >> DNA-PK

信号通路 >> PI3K/Akt/mTOR 信号通路 >> PI3K

信号通路 >> 细胞周期/DNA损伤 >> 酪蛋白激酶

信号通路 >> PI3K/Akt/mTOR 信号通路 >> DNA-PK

信号通路 >> 干细胞及 Wnt 通路 >> 酪蛋白激酶

[ 靶点 ]

CK2:0.098 μM (IC50)

CK2α2:3.869 μM (IC50)

[体外研究]

LY294002盐酸盐(0-75μM；24小时和48小时)以剂量依赖性方式显著减少人鼻咽癌CNE-2Z细胞[4]。LY294002盐酸盐(0-75μM；24小时和48小时)诱导CNE-2Z细胞凋亡率呈剂量依赖性[4]。LY294002盐酸盐(10-75μM)显著降低CNE-2Z细胞中p-Akt(S473)的表达水平并上调caspase-9活性。不同浓度的Akt总蛋白水平没有差异[4]。LY294002盐酸盐(5、10100µM；持续2小时)治疗部分抑制溶血磷脂酸(LPA)诱导的(20µM,持续4小时)YAP核易位,同时降低p-AKT水平[6]。细胞增殖试验细胞系：CNE-2Z细胞[4]浓度：0μM、10μM、25μM、50μM和75μM孵育时间：24小时和48小时结果：CNE-2Z细胞呈剂量依赖性减少。凋亡分析细胞系：CNE-2Z细胞[4]浓度：0μM、10μM、25μM、50μM和75μM培养时间：24小时和48小时结果：诱导凋亡率呈剂量依赖性。Western Blot分析细胞系：CNE-2Z细胞[4]浓度：0μM、10μM、25μM、50μM和75μM孵育时间：24小时和48小时结果：治疗组中磷酸化Akt(S473)表达水平显著降低,半胱天冬酶-9活性上调。

[体内研究]

LY294002盐酸盐(10、25、50、75 mg/kg；静脉注射；每周两次；持续4周)以剂量依赖性方式显著降低平均鼻咽癌肿瘤负担。LY294002(10,25 mg/kg)在降低肿瘤负担方面效果较差[4]。LY294002盐酸盐(每天1.2毫克/千克；静脉注射；持续14天)可预防瘦素(60微克/千克)对Sprague-Dawley大鼠精子的不良影响[5]。动物模型：裸鼠(6-8周),CNE-2Z异种移植[4]剂量：10 mg/kg、25 mg/kg,50 mg/kg和75 mg/kg给药：IP；结果：平均鼻咽癌(NPC)肿瘤负荷以剂量依赖性方式显著降低。

[参考文献]

[1]. Bai R, et al. The effect of PI3K inhibitor LY294002 and gemcitabine hydrochloride combined with ionizing radiation on the formation of vasculogenic mimicry of Panc-1 cells in vitro and in vivo. Neoplasma. 2016;63(1):80-92.

[2]. Chaussade C, et al. Evidence for functional redundancy of class IA PI3K isoforms in insulin signalling. Biochem J. 2007 Jun 15;404(3):449-58.

[3]. Gharbi SI, et al. Exploring the specificity of the PI3K family inhibitor LY294002. Biochem J. 2007 May 15;404(1):15-21.

[4]. Jiang H, et al. Phosphatidylinositol 3-kinase inhibitor(LY294002) induces apoptosis of human nasopharyngeal carcinoma invitro and in vivo. J Exp Clin Cancer Res. 2010 Apr 22;29:34.

[5]. Md Mokhtar AH, et al. LY294002, a PI3K pathway inhibitor, prevents leptin-induced adverse effects on spermatozoa in Sprague-Dawley rats. Andrologia. 2019 Apr;51(3):e13196.

[6]. Yi-Jen Hsueh, et al. Lysophosphatidic acid induces YAP-promoted proliferation of human corneal endothelial cells via PI3K and ROCK pathways. Mol Ther Methods Clin Dev. 2015 Apr 29;2:15014.

LY-294,002 盐酸盐物理化学性质

[ 分子式 ]:
C₁₉H₁₈ClNO₃

[ 分子量 ]:
343.80400

[ 精确质量 ]:
343.09800

[ PSA ]:
42.68000

[ LogP ]:
4.16360

[ 外观性状 ]:
白色至类白色固体

[ 储存条件 ]:
2-8°C

LY-294,002 盐酸盐MSDS

详细MSDS(安全技术说明书)

LY-294,002 盐酸盐安全信息

[ 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

LY-294,002 盐酸盐文献

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