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Ki16425

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Chemical Structure| 355025-24-0 同义名 : Debio 0719
CAS号 : 355025-24-0
货号 : A114375
分子式 : C23H23ClN2O5S
纯度 : 99%+
分子量 : 474.957
MDL号 : MFCD06798341
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(221.07 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • LPA2

    LPA2, Ki:6.5 μM

  • LPA1

    LPA1, Ki:0.34 μM

  • LPA3

    LPA3, Ki:0.93 μM
描述 LPA (lysophosphatidic acid), which has been shown to be involved in certain diseases such as atherosclerosis and cancer, can act through its receptor like LPA receptor 1, LPA receptor 2, or LPA receptor 3 and elicit different biological actions, like Ca2+ mobilization, changing in cAMP accumulation, changing cell shape and motility, and cell proliferation. Ki16425 is a LPA receptor antagonist with Ki values of 0.34μM for mouse LPA receptor 1 and 0.93μM for human LPA receptor 3, but with much higher Ki value for human LPA receptor 2 (Ki=6.5μM). Pre-treatment with 1μM Ki16425 can inhibit LPA-induced [Ca22+]i increase in THP-1 cells and 3T3 fibroblasts. Also, Ki16425 could decrease the This LPA-induced response of inositol phosphate production in 3T3 fibroblasts and A431 cells, but not S1P3- or S1P2-expressing CHO cells, at concentration of 10μM. The cAMP accumulation inhibited by LPA in FRTL-5 thyroid cells in a PTX-sensitive manner could be almost completely suppressed by 10μM Ki16425. Cell proliferation and migration induced by LPA in Swiss 3T3 fibroblasts could be inhibited dose-dependently by Ki16425. Treatment with Ki16425 at dose of 10mg/kg intradermally could improve dermal and lung fibrosis in a mouse model of bleomycin-induced murine scleroderma. Pre-treatment with 10μM for 30 minutes could completely block LPA-induced YAP/TAZ phosphorylation and inhibit Hippo signaling pathway in HEK293A cells.
作用机制 Ki16425 can antagonize the binding of LPA to the receptor, thus competitively inhibiting LPA-induced GTP binding and LPA receptor binding to membrane fractions.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
CHOK1 cells Function assay Antagonist activity at human recombinant LPA1 receptor expressed in CHOK1 cells assessed as inhibition of lysophosphatidic acid-induced intracellular calcium influx, IC50=0.51 μM 17467986
HEK293 cells Function assay 5 mins Antagonist activity at human LPA1 receptor expressed in HEK293 cells assessed as inhibition of LPA-induced AP-TGF-alpha release treated 5 mins before LPA addition measured after 60 mins 22658556
human chem1 cells Function assay Antagonist activity at LPA1 expressed in human chem1 cells assessed as effect on intracellular calcium mobilization by FLIPR assay, IC50=0.046 μM 20056548
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.11mL

0.42mL

0.21mL

10.53mL

2.11mL

1.05mL

21.05mL

4.21mL

2.11mL
参考文献

[1]Ohta H, Sato K, et al. Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Mol Pharmacol. 2003 Oct;64(4):994-1005.

[2]Ohashi T, Yamamoto T, et al. Antifibrotic effect of lysophosphatidic acid receptors LPA1 and LPA3 antagonist on experimental murine scleroderma induced by bleomycin. Exp Dermatol. 2015 Sep;24(9):698-702.

[3]Yu FX, Zhao B, et al. Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell. 2012 Aug 17;150(4):780-91.

[4]Sánchez-Marín L, Ladrón de Guevara-Miranda D, et al. Systemic blockade of LPA1/3 lysophosphatidic acid receptors by ki16425 modulates the effects of ethanol on the brain and behavior. Neuropharmacology. 2018 May 1;133:189-201.

[5]David M, Ribeiro J, et al. Targeting lysophosphatidic acid receptor type 1 with Debio 0719 inhibits spontaneous metastasis dissemination of breast cancer cells independently of cell proliferation and angiogenesis. Int J Oncol. 2012 Apr;40(4):1133-41.