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Ki16425

现货
Catalog No.
A1987
LPA受体拮抗剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
5mg
¥ 500.00
现货
25mg
¥ 2,000.00
现货
100mg
¥ 4,500.00
现货

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Background

Ki16425 is a subtype-selective antagonist of lysophosphatidic acid receptor (LPA) with Ki values of 0.34 μM for LPA1, 6.5μM for LPA2, and 0.93μM for LPA3 [4].

It has been reported that Ki16425 inhibited the LPA receptor-mediated actions in the order of LPA1≥LPA3≥LPA2. Ki16425 inhibited LPA-induced guanosine 5’-O-(3-thio) triphosphate binding, membrane fractions binding, and was involved in the long-term responses, including DNA synthesis and cell migration [1]. Ki16425 attenuated LPA-mediated intracellular signaling and invasion responses in vitro. Co-treatment of Ki16425 and sunitinib prolonged the sensitivity of renal tumor cell to sunitinib in xenograft mouse models [3]. In human breast cancer cells, Ki16425 can inhibit heparin-binding EGF-like growth factor (HB-EGF) expression [4].

In mouse thoracic aorta, Ki16425 significantly reduced LPA-induced vasorelaxation [2]. Ki16425 treatment also blocked renal tumorigenesis in vivo [3]. A five-day treatment with Ki16425 significantly decreased both HB-EGF mRNA expression at the transplanted tumor site in mice and circulating human HB-EGF concentrations in serum [4].

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]. Ruisanchez É, 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.

文献引用

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

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt474.96
Cas No.355025-24-0
FormulaC23H23ClN2O5S
Solubility≥23.75mg/mL in DMSO
Chemical Name3-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]methylsulfanyl]propanoic acid
SDFDownload SDF
Canonical SMILESCC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)CSCCC(=O)O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

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.

生物活性

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

化学结构

Ki16425

相关生物数据

Ki16425

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Ki16425

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Ki16425

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Ki16425