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]。