Ki16198
目录号 : GC15062
Ki16198 是一种有效且具有口服活性的 LPA 受体拮抗剂，即 Ki16425 的甲酯。 Ki16198 抑制 LPA1 和 LPA3 诱导的磷酸肌醇产生，Ki 值分别为 0.34 μM 和 0.93 μM。 Ki16198 对体内胰腺癌的肿瘤发生和转移有效。
Cas No.:355025-13-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
|
Inositolphosphate response |
RH7777 cells expressing LPA1, LPA2, LPA3, LPA4, or LPA5 were cultured on collagen-coated 12-well dishes in the growth medium, and then the medium was changed to TCM199 containing 2 μCi/mL [3H]inositol and 0.1% (w/v) BSA (fraction V). After 24 hrs, the cells were washed 3 times with HEPES-buffered medium, which consisted of 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 glucose, and 0.1% (w/v) BSA, and incubated for 30 mins with the indicated concentrations of Ki16198 with or without 1 μM LPA in the presence of 10 mM LiCl in the same medium at final volume of 0.5 mL. The reaction was terminated by adding 1 N HCl (0.1 mL) and freezing the cells. The supernatant (acid extract in 0.5 mL) of the thawed cells was used for the separation of [3H]inositol phosphate fractions. The results were normalized to 105 dpm of the total radioactivity incorporated into the cellular inositol lipids. The radioactivity of the trichloroacetic acid (5%)-insoluble fraction was measured as the total radioactivity. |
| Cell experiment [1]: | |
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Cell lines |
YAPC-PD cells |
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Preparation method |
The solubility of this compound in DMSO is > 24.5 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
10 μM; 24 hrs |
|
Applications |
In YAPC-PD cells, Ki16198 inhibited LPA-mediated migration and invasion. Moreover, Ki16198 inhibited LPA-induced expression of proMMP-9 protein and mRNA. |
| Animal experiment [1]: | |
|
Animal models |
Mice bearing YAPC-PD xenografts |
|
Dosage form |
2 mg/kg; p.o. |
|
Applications |
In mice bearing YAPC-PD xenografts, Ki16198 (2 mg/kg) substantially decreased the total metastatic node weight in the peritoneal cavity, as well as ascites formation by 50%. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
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. | |
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.
| Cas No. | 355025-13-7 | SDF | |
| 化学名 | methyl 3-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]methylsulfanyl]propanoate | ||
| Canonical SMILES | CC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)CSCCC(=O)OC | ||
| 分子式 | C24H25ClN2O5S | 分子量 | 488.98 |
| 溶解度 | ≥ 24.45mg/mL in DMSO | 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0451 mL | 10.2254 mL | 20.4507 mL |
| 5 mM | 0.409 mL | 2.0451 mL | 4.0901 mL |
| 10 mM | 0.2045 mL | 1.0225 mL | 2.0451 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。