Ki16425
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Ki16425是溶血磷脂酸受体（LPA）的亚型选择性拮抗剂，对LPA1、LPA2和LPA3受体的Ki值分别为0.34、6.5和0.93 M[4]。
据报道，Ki16425对LPA受体介导应答的抑制强度为LPA1≥LPA3≥LPA2。Ki16425抑制LPA诱导的鸟苷5'-O-(3-硫代三磷酸)结合和膜成分结合，并参与各种持续应答，包括DNA合成和细胞迁移[1]。Ki16425体外减弱LPA介导的细胞内信号传导和侵袭响应。在异种移植小鼠模型中，联合使用Ki16425和Sunitinib延长肾肿瘤细胞对Sunitinib的敏感性[3]。在人乳腺癌细胞中，Ki16425能抑制肝素结合EGF样生长因子（HB-EGF）的表达[4]。
在小鼠胸主动脉中，Ki16425显著降低LPA诱导的血管舒张[2]。Ki16425治疗也可以阻止体内肾肿瘤的发生[3]。给予Ki16425，持续5天，可以显著减少小鼠肿瘤移植部位HB-EGF mRNA的表达以及人HB-EGF的血清浓度[4]。
参考文献：
[1]. Ohta H, Sato K, Murata N, Damirin A, Malchinkhuu E, Kon J, Kimura T, Tobo M, Yamazaki Y, Watanabe T, Yagi M, Sato M, Suzuki R, Murooka H, Sakai T, Nishitoba T, Im DS, Nochi H, Tamoto K, Tomura H, Okajima F. Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Mol Pharmacol. 2003 Oct;64(4):994-1005.
[2]. Ruisanchez , Dancs P, Kerék M, Németh T, Faragó B, Balogh A, Patil R, Jennings BL, Liliom K, Malik KU, Smrcka AV, Tigyi G, Benyó Z. Lysophosphatidic acid induces vasodilation mediated by LPA1 receptors, phospholipase C, and endothelial nitric oxide synthase. FASEB J. 2014 Feb;28(2):880-90.
[3]. Su SC, Hu X, Kenney PA, Merrill MM, Babaian KN, Zhang XY, Maity T, Yang SF, Lin X, Wood CG. Autotaxin-lysophosphatidic acid signaling axis mediates tumorigenesis and development of acquired resistance to sunitinib in renal cell carcinoma. Clin Cancer Res. 2013 Dec 1;19(23):6461-72.
[4]. David M, Sahay D, Mege F, Descotes F, Leblanc R, Ribeiro J, Clézardin P, Peyruchaud O. Identification of Heparin-Binding EGF-Like Growth Factor (HB-EGF) as a Biomarker for Lysophosphatidic Acid Receptor Type 1 (LPA1) Activation in Human Breast and Prostate Cancers. PLoS One. 2014 May 14;9(5):e97771.
- 1.Moreno-Fernández RD, Nieto-Quero A, et al. "Effects of genetic deletion versus pharmacological blockade of the LPA(1) receptor on depression-like behaviour and related brain functional activity." Dis Model Mech. 2018 Jul 30. pii: dmm.035519. PMID:30061118
- 2.Sánchez-Marín L, Ladrón de Guevara-Miranda D, et al. "Systemic blockade of LPA(1/3) lysophosphatidic acid receptors by ki16425 modulates the effects of ethanol on the brain and behavior." Neuropharmacology. 2018 May 1;133:189-201. PMID:29378212
- 3.Ladrón de Guevara-Miranda D, Moreno-Fernández RD, et al." Lysophosphatidic acid-induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine-contextual memory."Addict Biol. 2018 Feb 26. PMID:29480526
- 4.Loskutov YV, Griffin CL, et al. "LPA signaling is regulated through the primary cilium:a novel target in glioblastoma." Oncogene. 2018 Jan 11. PMID:29321663
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 474.96 |
| Cas No. | 355025-24-0 |
| Formula | C23H23ClN2O5S |
| Solubility | ≥23.75 mg/mL in DMSO; insoluble in H2O; ≥12.54 mg/mL in EtOH |
| Chemical Name | 3-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]methylsulfanyl]propanoic acid |
| SDF | Download SDF |
| Canonical SMILES | CC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)CSCCC(=O)O |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 激酶实验 [1]: | |
|
肌醇磷酸生成 |
将RH7777细胞置于含或不含Ki16425的培养液中孵育1分钟，并测定肌醇磷酸（肌醇二磷酸和肌醇三磷酸的总和）含量。将结果标准化为结合到细胞肌醇脂类的总放射性（105 dpm），并将三氯乙酸（5%）的放射性（不溶解部分）作为总放射性。 |
| 细胞实验 [2]: | |
|
细胞系 |
MDA-MB-231细胞和PC3细胞 |
|
制备方法 |
在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液，一般步骤如下：请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
|
反应条件 |
10 μM；45分钟或24小时 |
|
试验结果 |
在人乳腺癌和前列腺癌细胞中，Ki16425抑制肝素结合EGF样生长因子（HB-EGF）的表达。 |
| 动物实验 [2]: | |
|
动物模型 |
PC3细胞异种移植小鼠模型 |
|
给药剂量 |
25 mg/kg；皮下注射；持续5天 |
|
实验结果 |
在PC3细胞异种移植小鼠模型中，为期5天的Ki16425治疗显著下调移植肿瘤部位的HB-EGF mRNA表达以及循环血清中的人HB-EGF水平。 |
|
其他注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同，但仍处于实验系统误差的允许范围内。 |
|
References: [1]. Ohta H, Sato K, Murata N, Damirin A, Malchinkhuu E, Kon J, Kimura T, Tobo M, Yamazaki Y, Watanabe T, Yagi M, Sato M, Suzuki R, Murooka H, Sakai T, Nishitoba T, Im DS, Nochi H, Tamoto K, Tomura H, Okajima F. Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Mol Pharmacol. 2003 Oct;64(4):994-1005. [2]. David M, Sahay D, Mege F, Descotes F, Leblanc R, Ribeiro J, Clézardin P, Peyruchaud O. Identification of Heparin-Binding EGF-Like Growth Factor (HB-EGF) as a Biomarker for Lysophosphatidic Acid Receptor Type 1 (LPA1) Activation in Human Breast and Prostate Cancers. PLoS One. 2014 May 14;9(5):e97771. |
|
| Description | Ki16425是LPA受体的拮抗剂，对人LPA1、LPA2和LPA3受体的Ki值分别为0.34、6.5和0.93 ?M。 | |||||
| 靶点 | human LPA1 | human LPA2 | human LPA3 | |||
| IC50 | 0.34 ?M | 6.5 ?M | 0.93 ?M | |||
质量控制和MSDS
- 批次:
化学结构
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