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Ki16198

现货
Catalog No.
B1591
LPA拮抗剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 3,710.00
现货
5mg
¥ 1,890.00
现货
10mg
¥ 2,590.00
现货
50mg
¥ 7,490.00
现货
200mg
¥ 17,290.00
Ship with 10-15 days

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Background

Ki16198 is the methyl ester of Ki16425. Ki16198, a LPA antagonist, inhibits LPA1- and LPA3-induced inositol phosphate production with the Ki of 0.34 μM and 0.93 μM, respectively, shows weaker inhibition for LPA2, no activity at LPA4, LPA5, LPA6[1].

Lysophosphatidic acid (LPA) is an extracellular signaling lipid involved in regulating cell proliferation, survival, and motility of normal and cancer cells[2].

In vitro: In YAPC-PD cancer cell line, Ki16198 substantially inhibited LPA1- and LPA3-mediated responses with low potency to LPA2 and no activity to LPA4, LPA5 and LPA6. Treatment with Ki16198 (10 μM) effectively inhibited migration and invasion responses to LPA in YAPC-PD cancer cell line. Incubation of Ki16198 (10 μM) inhibited the LPA-induced expression of proMMP-9 protein and mRNA in YAPC-PD cells [1].Administration of Ki16198 (1 μM) inhibited the proliferation of lpa1Δ-1 and lpa1Δ+-1 cells by about 70% [2].

In vivo: In YAPC-PD pancreatic cancer cell-inoculated nude xenograft mouse model, Oral administration of Ki16198 (2 mg/kg) significantly inhibited tumor weight and remarkably attenuated invasion and metastasis to lung, liver, and brain and decreased the total metastatic node weight in the peritoneal cavity and ascites formation by 50% [1].Oral administration of Ki16198 (60 mg/kg) significantly inhibited lactate-induced limb lesions in rats [3].

References:
[1].  Komachi M, Sato K, Tobo M, et al. Orally active lysophosphatidic acid receptor antagonist attenuates pancreatic cancer invasion and metastasis in vivo[J]. Cancer science, 2012, 103(6): 1099-1104.
[2].  Shano S, Hatanaka K, Ninose S, et al. A lysophosphatidic acid receptor lacking the PDZ-binding domain is constitutively active and stimulates cell proliferation[J]. BiochimicaetBiophysicaActa (BBA)-Molecular Cell Research, 2008, 1783(5): 748-759.
[3].  Kimura T, Mogi C, Sato K, et al. p2y5/LPA6 attenuates LPA1-mediated VE-cadherin translocation and cell–cell dissociation through G12/13 protein–Src–Rap1[J]. Cardiovascular research, 2011: cvr154.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt488.98
Cas No.355025-13-7
FormulaC24H25ClN2O5S
Solubility≥24.45mg/mL in DMSO
Chemical Namemethyl 3-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]methylsulfanyl]propanoate
SDFDownload SDF
Canonical SMILESCC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)CSCCC(=O)OC
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]:

磷酸肌醇反应

将表达LPA1、LPA2、LPA3、LPA4或LPA5的RH7777细胞置于胶原包被的12孔板上培养,加入细胞生长培养液。然后,将培养液换成含2 μCi/mL [3H]肌醇和0.1% (w/v) BSA(组分 V)的TCM199。24小时后,使用HEPES缓冲液洗涤细胞3次。缓冲液含20 mM Hepes (pH 7.4),134 mM NaCl,4.7 mM KCl,1.2 mM KH2PO4,1.2 mM MgSO4,2 mM CaCl2,2.5 mM NaHCO3,5 mM葡萄糖以及0.1% (w/v) BSA。将其与指定浓度的Ki16198一起孵育30分钟,加入或不加入LPA,加入10 mM LiCl,反应体系终体积为0.5 mL。加入1 N HCl (0.1 mL),冷冻细胞,终止反应,使用解冻细胞的上清液(0.5mL酸提取液)分离[3H]磷酸肌醇组分。结果归一化到掺入细胞肌醇脂质总放射性的105 dpm。三氯乙酸 (5%) 不溶部分的放射性作为总放射性。

细胞实验 [1]:

细胞系

YAPC-PD细胞

制备方法

在DMSO中的溶解度大于24.5 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C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 °C可放置数月。

反应条件

10 μM;24小时

实验结果

在YAPC-PD细胞中,Ki16198抑制LPA介导的迁移和侵袭。此外,Ki16198抑制LPA诱导的proMMP-9蛋白和mRNA表达。

动物实验 [1]:

动物模型

携带YAPC-PD细胞异种移植瘤的小鼠

给药剂量

2 mg/kg;口服给药

实验结果

在携带YAPC-PD细胞异种移植瘤的小鼠中,Ki16198 (2 mg/kg) 显著降低腹腔总转移淋巴结重量,并抑制50%的腹水形成。

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]. Komachi M, Sato K, Tobo M, et al. Orally active lysophosphatidic acid receptor antagonist attenuates pancreatic cancer invasion and metastasis in vivo[J]. Cancer science, 2012, 103(6): 1099-1104.

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