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.