Ki16425
(Synonyms: Debio 0719) 目录号 : GC11374
Ki16425是溶血磷脂酸受体 LPA1 和 LPA3 的拮抗剂，Ki 值分别为 0.25 和 0.36μM。Ki16425 可降低 LPA 诱导的 p42/p44 MAPK 的活化，阻断 LPA 诱导的是相关蛋白（YAP）和含 WW 结构域的转录调节蛋白 1（TAZ）的去磷酸化，从而抑制 Hippo 信号通路。
Cas No.:355025-24-0
Sample solution is provided at 25 µL, 10mM.
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Ki16425 is an antagonist of the lysophosphatidic acid receptors LPA1 and LPA3 and Ki values are 0.25 and 0.36μM respectly. Ki16425 reduces the LPA-induced activation of p42/p44 MAPK.Blocks LPA-induced dephosphorylation of Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (TAZ), inhibiting the Hippo signaling pathway [1].
Ki1642 (10μM; 24h) decreases lysophosphatidic acid (LPA)-induced HaCaT cell proliferation[2].LPA increased IL-17 mRNA expression in a dose-dependent manner, while the LPA inhibitor Ki16425 (10μM; 24h) suppressed this response[2]. Ki16425 (10μM; 120min) treatment suppressed LPA-induced ROCK2 and p38 MAPK expression[3].
Ki16425 (15mg/kg; ip; 7days) decreases the Epidermal Expression of ROCK2 and p-AKT in Imiquimod-Induced Psoriasis-like Mice)[2].Ki16425 (15mg/kg; ip; 4weeks ) treatment reduced serum IL-17 levels and IL-17 expression in exocrine glands in an adoptive transfer model[3].Ki16425 blocked the damage to the intestinal barrier of mice caused by Escherichia coli after LPA 1 signaling in the host[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].Kim D, Kim HJ, Baek JO, Roh JY, Jun HS. Lysophosphatidic Acid Mediates Imiquimod-Induced Psoriasis-like Symptoms by Promoting Keratinocyte Proliferation through LPAR1/ROCK2/PI3K/AKT Signaling Pathway. Int J Mol Sci. 2021 Oct 5;22(19):10777.
[3].Park E, Kim D, Lee SM, Jun HS. Inhibition of lysophosphatidic acid receptor ameliorates Sjögren's syndrome in NOD mice. Oncotarget. 2017 Apr 18;8(16):27240-27251.
[4]. Zou D, Pei J, Lan J, Sang H, Chen H, Yuan H, Wu D, Zhang Y, Wang Y, Wang D, Zou Y, Chen D, Ren J, Gao X, Lin Z. A SNP of bacterial blc disturbs gut lysophospholipid homeostasis and induces inflammation through epithelial barrier disruption.
Ki16425是溶血磷脂酸受体 LPA1 和 LPA3 的拮抗剂，Ki 值分别为 0.25 和 0.36μM。Ki16425 可降低 LPA 诱导的 p42/p44 MAPK 的活化，阻断 LPA 诱导的是相关蛋白（YAP）和含 WW 结构域的转录调节蛋白 1（TAZ）的去磷酸化，从而抑制 Hippo 信号通路[1]。
Ki16425 ( 10μM；24h ) 能降低溶血磷脂酸（LPA）诱导的 HaCaT 细胞增殖[2]。LPA 能以剂量依赖的方式增加 IL-17 mRNA 的表达，而 LPA 抑制剂 Ki16425 ( 10μM；24h ) 能抑制这种反应[2]。Ki16425（10μM；120min）抑制了 LPA 诱导的 ROCK2 和 p38 MAPK 的表达[3]。
Ki16425 (15mg/kg；ip；7days) 可降低Imiquimod 诱导的类牛皮癣小鼠表皮的 ROCK2 和 p-AKT 表达[2]。Ki16425（15mg/kg；ip；4weeks）治疗可降低过继转移模型中血清 IL-17 水平和外分泌腺中 IL-17 的表达[3]。Ki16425 可阻断大肠杆菌在宿主体内发出 LPA 1 信号后对小鼠肠道屏障造成的破坏[4]。
| Cell experiment [1]: | |
Cell lines | HaCaT cells |
Preparation Method | HaCaT cells were treated with or without 10μM LPA and ki16425 (10μM ) concentration for 24 h, and cell viability was examined by CCK8 assay. |
Reaction Conditions | Ki16425:10μM; 24h |
Applications | Ki16425 (10μM; 24h) decreases lysophosphatidic acid (LPA)-induced HaCaT cell proliferation. |
| Animal experiment [2]: | |
Animal models | Colon epithelial barrier disruption model |
Preparation Method | Ki16425 was injected into mice before E. coli BW25113 or blcE84 infection. Control groups received the same volume of DMSO. |
Dosage form | Ki16425:20mg/kg; ip; 24h |
Applications | Ki16425 blocked the damage to the intestinal barrier of mice caused by Escherichia coli after LPA 1 signaling in the host. |
References: | |
| 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。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet