LY 294002
(Synonyms: LY294002/PI3K抑制剂) 目录号 : GC15485
LY294002是第一个合成的PI3Kα、δ和β抑制剂。
Cas No.:154447-36-6
Sample solution is provided at 25 µL, 10mM.
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LY294002, a well-known PI3K signaling pathway inhibitor, is the first synthetic PI3Kα, δ and β inhibitor with IC50 of 500nM, 570nM and 970nM, respectively. LY294002 is not exclusively selective for the PI3Ks, and could in fact act on other lipid kinases and additional apparently unrelated proteins[1]
When LY294002 was added to NPC cells with different concentrations, levels of phosphorylation (S473) Akt were decreased in treated NPC cells, exhibiting a dose-response effect. LY294002 markedly inhibited NPC CNE-2Z cell growth, proliferation, and induced apoptosis in vitro and in vivo[2]. The PI3k/AKT pathway is constitutively activated in a majority of human pancreatic cancer cell lines and the pathway is a promising target for therapeutic intervention. LY294002 produce apoptosis and antiproliferative effects on pancreatic carcinoma cells in vivo and in vitro[3]
LY294002(1.2 mg/kg) was given together with leptin (60 µg/kg) once daily for 14 days via the intraperitoneal (i.p.) route. The result found that body weight in leptin+LY294002-treated rats decreased significantly and STEH was higher (p < 0.001). Ratio of testicular phosphor-Akt/total Akt was significantly higher in leptin+LY294002-treated rats (p < 0.001). The adverse effects of leptin were prevented by concurrent administration of LY294002, suggest the potential involvement of the PI3K signaling pathway in leptin-induced detrimental effects on spermatozoa[4]
LY294002是一种著名的PI3K信号通路抑制剂，是第一个具有IC50分别为500nM、570nM和970nM的合成PI3Kα、δ和β抑制剂。LY294002并不完全选择性地作用于PI3Ks，并且实际上可能对其他脂质激酶和额外看似无关的蛋白质产生影响。
当不同浓度的LY294002添加到NPC细胞中时，处理后的NPC细胞中磷酸化（S473）Akt水平降低，呈现剂量反应效应。LY294002显著抑制了NPC CNE-2Z细胞在体外和体内的生长、增殖，并诱导凋亡[2]。PI3k/AKT通路在大多数人类胰腺癌细胞系中被恒定激活，该通路是治疗干预的有前途靶点。LY294002对体内和体外的胰腺癌细胞产生凋亡和抗增殖作用[3]。
在腹腔注射途径下，每天给予LY294002（1.2毫克/千克）和瘦素（60微克/千克），连续14天。结果发现，在接受瘦素+LY294002处理的大鼠中，体重显著降低，并且精子头部顶端反应时间更长（p[4]。
References:
[1]. Gharbi SI, Zvelebil MJ, et al. Exploring the specificity of the PI3K family inhibitor LY294002. Biochem J. 2007 May 15;404(1):15-21.
[2]. Jiang H, Fan D, et al. Phosphatidylinositol 3-kinase inhibitor (LY294002) induces apoptosis of human nasopharyngeal carcinoma in vitro and in vivo. J Exp Clin Cancer Res. 2010 Apr 22;29(1):34.
[3]. Bondar VM, Sweeney-Gotsch B, et al. Inhibition of the phosphatidylinositol 3'-kinase-AKT pathway induces apoptosis in pancreatic carcinoma cells in vitro and in vivo. Mol Cancer Ther. 2002 Oct;1(12):989-97. PMID: 12481421.
[4]. Almabhouh FA, et al. LY294002, a PI3K pathway inhibitor, prevents leptin-induced adverse effects on spermatozoa in Sprague-Dawley rats. Andrologia. 2019 Apr;51(3):e13196.
| Kinase experiment [1]: | |
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Preparation Method |
PI3K inhibition by LY294002 was determined in a radiometric assay using purified, recombinant enzymes (class IA and class IB) with 1 µM ATP. The kinase reaction was carried out for 1 h at room temperature (24 ℃) and was terminated by addition of PBS. |
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Reaction Conditions |
10µM, 1 h at room temperature |
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Applications |
LY294002 not only binds to class I PI3Ks and other PI3K-related kinases, but also to novel targets unrelated to the PI3K family. |
| Cell experiment [2]: | |
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Cell lines |
K562 |
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Reaction Conditions |
10µM/L，incubate for 24 and 48h at 37 ℃, 5% CO2 |
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Applications |
LY294002 and DNR were able to inhibit the growth of K562 cells and promote apoptosis in time- and concentration-dependent manner (P＜0.05), both the cell proliferation-inhibiting rate and apoptosis rate in combination therapy group were higher than that in DNR-monotherapy group (P＜0.05). After K562 cells treated by LY294002 combined DNR for 36 h, the cells were statistically significantly reduced in G2/M phase (P＜0.05), as compared with control group and DNR group. Compared with DNR group, the cell level of G0/G1 phase raised (P＜0.05) and cell level of S phase decreased (P＞0.05). Compared with DNR group, the expression of SKP2 and BCL-2 mRNA decreased, and the expression of P27 mRNA increased in the combination therapy group (P＜0.05). |
| Animal experiment [3]: | |
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Animal models |
Male Wistar rats, weighting 180~200g |
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Preparation Method |
Rats were randomly separated into four groups (with 10 rats in each group): control group, DOI treated group, DOI treated with tiapride group, DOI treated with LY294002 group. Tourette Syndrome was induced in rats by DOI intraperitoneal injection at dosage of 1 mg/kg, once daily for 21 days continuously. |
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Dosage form |
25µg/kg dissolved in 10% dimethyl sulfoxide，intracerebroventricularly injected |
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Applications |
LY294002 treatment significantly relieved Tourette syndrome induced by DOI, 5HT2A/c receptor agonist and reduced PI3K/Akt/NF-κB mediated neuroinflammation. |
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References: [1]. Gharbi SI, Zvelebil MJ, et al. Exploring the specificity of the PI3K family inhibitor LY294002. Biochem J. 2007 May 15;404(1):15-21. [2]. Geng YH, Wu WJ, et al. LY294002 Enhaces Chemosensitivity of K562 Cells to Daunorubicin. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Feb;28(1):110-118. [3]. Hongyan L, et al. LY294002, a PI3K inhibitor, attenuates Tourette syndrome in rats. Metab Brain Dis. 2017 Oct;32(5):1619-1625. |
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| Cas No. | 154447-36-6 | SDF | |
| 别名 | LY294002/PI3K抑制剂 | ||
| 化学名 | 2-morpholin-4-yl-8-phenylchromen-4-one | ||
| Canonical SMILES | C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC=C4 | ||
| 分子式 | C19H17NO3 | 分子量 | 307.34 |
| 溶解度 | ≥ 40.37mg/mL in DMSO, ≥ 13.55mg/mL in EtOH | 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 | 3.2537 mL | 16.2686 mL | 32.5373 mL |
| 5 mM | 0.6507 mL | 3.2537 mL | 6.5075 mL |
| 10 mM | 0.3254 mL | 1.6269 mL | 3.2537 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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