LYG-202
目录号 : GC40865
A synthetic flavonoid with anticancer and anti-angiogenic activities
Cas No.:1175077-25-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
LYG-202 is a synthetic flavonoid with anticancer and anti-angiogenic activities. It inhibits proliferation of HepG2, MCF-7, HeLa, BGC-823, MDA-MB-435, and HCT116 cancer cells in vitro (IC50s = 4.74-27.70 μM) via induction of apoptosis and dissipation of the mitochondrial membrane potential. LYG-202 reduces tumor growth in S180 sarcoma cell-inoculated mice. It also inhibits VEGF-stimulated human umbilical vein endothelial cells (HUVEC) cell migration and tube formation in vitro and decreases capillary sprouting in isolated rat aortic rings and the chicken chorioallantoic membrane (CAM) model of angiogenesis.
| Cas No. | 1175077-25-4 | SDF | |
| Canonical SMILES | CN1CCN(CCCCOC2=CC(O)=C(C(C=C(C3=CC=CC=C3)O4)=O)C4=C2OC)CC1 | ||
| 分子式 | C25H30N2O5 | 分子量 | 438.5 |
| 溶解度 | DMF: 14 mg/ml,DMF:PBS (pH7.2) (1:40): 0.12 mg/ml,Ethanol: 2.5 mg/ml | 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 | 2.2805 mL | 11.4025 mL | 22.805 mL |
| 5 mM | 0.4561 mL | 2.2805 mL | 4.561 mL |
| 10 mM | 0.2281 mL | 1.1403 mL | 2.2805 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。
LYG-202 exerts antitumor effect on PI3K/Akt signaling pathway in human breast cancer cells
Apoptosis 2015 Sep;20(9):1253-69.PMID:26153346DOI:10.1007/s10495-015-1145-x.
In this study, we aimed to investigate the antitumor effect of LYG-202, a newly synthesized piperazine-substituted derivative of flavonoid on human breast cancer cells and illustrate the potential mechanisms. LYG-202 induced apoptosis in MCF-7, MDA-MB-231 and MDA-MB-435 cells. LYG-202 triggered the activation of mitochondrial apoptotic pathway through multiple steps: increasing Bax/Bcl-2 ratio, decreasing mitochondrial membrane potential (ΔΨ(m)), activating caspase-9 and caspase-3, inducing cleavage of poly(ADP-ribose) polymerase, cytochrome c release and apoptosis-inducing factor translocation. Furthermore, LYG-202 inhibited cell cycle progression at the G1/S transition via targeting Cyclin D, CDK4 and p21(Waf1/Cip1). Additionally, LYG-202 increased the generation of intracellular ROS. N-Acetyl cysteine, an antioxidant, reversed LYG-202-induced apoptosis suggesting that LYG-202 induces apoptosis by accelerating ROS generation. Further, we found that LYG-202 deactivated the PI3K/Akt pathway, activated Bad phosphorylation, increased Cyclin D and Bcl-xL expression, and inhibited NF-κB nuclear translocation. Activation of PI3K/Akt pathway by IGF-1 attenuated LYG-202-induced apoptosis and cell cycle arrest. Our in vivo study showed that LYG-202 exhibited a potential antitumor effect in nude mice inoculated with MCF-7 tumor through similar mechanisms identified in cultured cells. In summary, our results demonstrated that LYG-202 induced apoptosis and cell cycle arrest via targeting PI3K/Akt pathway, indicating that LYG-202 is a potential anticancer agent for breast cancer.
LYG-202 inhibits activation of endothelial cells and angiogenesis through CXCL12/CXCR7 pathway in breast cancer
Carcinogenesis 2018 Apr 5;39(4):588-600.PMID:29390073DOI:10.1093/carcin/bgy007.
Angiogenesis is critical for the growth and metastasis of triple-negative breast cancer (TNBC) and its inhibition reduces the risk of progression of metastatic TNBC. In this study, we investigated that LYG-202, a flavonoid with a piperazine substitution, inhibited angiogenesis induced by conditioned media (CM) from MDA-MB-231 cells under hypoxia and revealed its underlying mechanism. The results showed that LYG-202 decreased CXCL12 secretion and CXCR7 expression, leading to suppression of its downstream ERK/AKT/nuclear factor kappa B (NF-κB) signaling, which eventually decreased the expression of MMP-2, MMP-9, RhoA and increased VE-cadherin expression in EA.hy 926 cells treated with CM from MDA-MB-231 cells under hypoxia. The decreased migration ability, increased cell adhesion and inhibited CXCR7 pathway by LYG-202 could also be reproduced in human umbilical vein endothelial cells. More importantly, LYG-202 also inhibited tumor angiogenesis and tumor growth of human breast cancer MDA-MB-231 cells in nude mice through CXCL12/CXCR7 pathway. In summary, LYG-202 is a potential agent to prohibit tumor angiogenesis through inhibiting the activation of endothelial cells.
LYG-202, a new flavonoid with a piperazine substitution, shows antitumor effects in vivo and in vitro
Biochem Biophys Res Commun 2009 Aug 7;385(4):551-6.PMID:19481059DOI:10.1016/j.bbrc.2009.05.099.
LYG-202 is a newly synthesized flavonoid with a piperazine substitution. We investigated the antitumor effect of LYG-202 in vivo and in vitro. We show that, LYG-202 significantly decreases tumor growth in mice inoculated with S180 sarcoma cells, compared with the control group. Meanwhile, the viabilities of various kinds of tumor cells were inhibited by LYG-202 with IC(50) values in the range of 4.80 to 27.70 microM. Then apoptosis induced by LYG-202 in HepG2 cells was characterized by DAPI staining and Annexin V/PI double staining and degradation of PARP was observed. Activation of the caspase cascade for both the extrinsic and intrinsic pathways was demonstrated, including caspase-8, -9, and -3. The results also showed that the expression of Bcl-2 protein decreased whereas that of Bax protein increased, leading to an increase of the Bax/Bcl-2 ratio. Our results demonstrated that LYG-202 exhibited strong antitumor effect in vivo and in vitro, involving with apoptosis induction.
LYG-202 augments tumor necrosis factor-α-induced apoptosis via attenuating casein kinase 2-dependent nuclear factor-κB pathway in HepG2 cells
Mol Pharmacol 2012 Nov;82(5):958-71.PMID:22909797DOI:10.1124/mol.112.079848.
Tumor necrosis factor-α (TNF-α) is being used as an antineoplastic agent in treatment regimens of patients with locally advanced solid tumors, but TNF-α alone is only marginally active. In clinical use, it is usually combined with other chemical agents to increase its tumor response rate. Our previous studies reported that LYG-202 (5-hydroxy-8-methoxy-7-(4-(4-methylpiperazin-1-yl)butoxy)-2-phenyl-4H-chromen-4-one), a synthesized flavonoid with a piperazine substitution, has antiproliferative, antiangiogenic, and proapoptotic activities in multiple cancer cell lines. Here we evaluated the antineoplastic effect of TNF-α and analyzed the mechanism underlying its combination with LYG-202. Our results indicated that LYG-202 significantly increased the cytostatic and proapoptotic activity of TNF-α in HepG2 cells and heightened the protein level of apoptosis-related genes including caspase-3, caspase-8/9, cleaved poly(ADP-ribose) polymerase, and Bid. The fact that LYG-202 had a fitness score similar to that of the casein kinase 2 (CK2) inhibitor naphthyridine-8-carboxylate (CX-4945) implied to us that it may serve as a potential candidate for CK2 inhibitor, and the kinase activity assay suggested that LYG-202 significantly inhibited CK2 activity. Moreover, the electrophoretic mobility shift assay and luciferase assay showed that LYG-202 blocked the TNF-α-induced nuclear factor-κB (NF-κB) survival signaling pathway primarily by inactivating protein kinase CK2. In murine xenograft models, we also found that LYG-202 enhanced TNF-α antineoplastic activity and inhibited CK2 activity and NF-κB-regulated antiapoptotic gene expression. All these results showed that LYG-202 enhanced TNF-α-induced apoptosis by attenuating the CK2-dependent NF-κB pathway and probably is a promising agent in combination with TNF-α.
LYG-202, a newly synthesized flavonoid, exhibits potent anti-angiogenic activity in vitro and in vivo
J Pharmacol Sci 2010;112(1):37-45.PMID:20093787DOI:10.1254/jphs.09213fp.
LYG-202 (C25H30N2O5) is a newly synthesized flavonoid that has been confirmed to possess an antitumor effect, but the mechanism is unclear. Our present study was performed to identify the anti-angiogenic activity of this novel compound in vitro and in vivo. LYG-202 inhibited vascular endothelial growth factor (VEGF) stimulated migration and tube formation of human umbilical vein endothelial cells and arrested microvessel outgrowth from rat aortic rings in vitro. Meanwhile, LYG-202 suppressed the neovascularization of Chicken Chorioallantoic Membrane in vivo. Mechanistic studies revealed that LYG-202 suppressed the VEGF-induced tyrosine phosphorylation of KDR/Flk-1 (VEGFR-2) as well as its downstream protein kinases activation, by decreasing phosphorylated forms of serine/threonine kinase Akt, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase. LYG-202 exerts anti-angiogenic activity both in vitro and in vivo, and these results suggest that it deserves further investigation as a promising anti-tumor angiogenesis compound.