Ki16425
(Synonyms: Debio 0719) 目录号 : GC11374
A selective LPA1 and LPA3 receptor antagonist
Cas No.:355025-24-0
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
| Kinase experiment [1]: | |
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Inositol phosphate production |
RH7777 cells are incubated for 1 min with or without Ki16425, and the inositol phosphates (sum of inositol bisphosphate and inositol trisphosphate) were measured. The results were normalized to 105 dpm of the total radioactivity incorporated into the cellular inositol lipids, and the radioactivity of trichloroacetic acid (5%)-insoluble fraction was considered as the total radioactivity. |
| Cell experiment [2]: | |
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Cell lines |
MDA-MB-231 and PC3 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reaction Conditions |
10 μM; 45 mins or 24 hrs |
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Applications |
In human breast and prostate cancer cells, Ki16425 inhibited heparin-binding EGF-like growth factor (HB-EGF) expression. |
| Animal experiment [2]: | |
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Animal models |
PC3 cell xenograft mouse model |
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Dosage form |
25 mg/kg; s.c.; for 5 days |
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Applications |
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. |
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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. |
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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. | |
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.
| Cas No. | 355025-24-0 | SDF | |
| 别名 | Debio 0719 | ||
| 化学名 | 3-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]methylsulfanyl]propanoic acid | ||
| Canonical SMILES | CC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)CSCCC(=O)O | ||
| 分子式 | C23H23ClN2O5S | 分子量 | 474.96 |
| 溶解度 | ≥ 23.75mg/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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1054 mL | 10.5272 mL | 21.0544 mL |
| 5 mM | 0.4211 mL | 2.1054 mL | 4.2109 mL |
| 10 mM | 0.2105 mL | 1.0527 mL | 2.1054 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。