Ki16198 is the methyl ester of Ki16425, which is a LPA antagonist and inhibits LPA1- and LPA3-induced inositol phosphate production with Ki of 0.34 μM and 0.93 μM, respectively, shows weaker inhibition for LPA2, no activity at LPA4, LPA5, LPA6.
Ki16198 is a potent and orally active antagonist of LPA receptors, functioning as the methyl ester derivative of Ki16425. It demonstrates efficacy in inhibiting LPA1 and LPA3-induced inositol phosphate production, with Ki values of 0.34 μM and 0.93 μM, respectively, showcasing its potential against pancreatic cancer tumorigenesis and metastasis when applied in vivo[1].
体内研究
Oral administration of Ki16198 (1 mg in 500 μl for 28 days) significantly reduces metastasis activity in treated mice, showing a notable decrease in metastatic spread to the liver, lungs, and brain. This highlights Ki16198's broad therapeutic potential in mitigating metastasis across multiple organ systems[1].
体外研究
In vitro experiments reveal that Ki16198, across a concentration range of 0 to 10 μM over 48 hours, effectively curtails migration and invasion responses to LPA in a manner comparable to Ki16425. Specifically, Ki16198 impacts the invasion response to LPA, without affecting responses to EGF, across various pancreatic cancer cell lines such as Panc-1, CFPAC-1, and BxPC-3[1].
At a concentration of 10 μM over 48 hours, Ki16198 markedly reduces both the protein and mRNA expression levels of proMMP-9 in YAPC-PD cells, indicating its role in modulating enzymes involved in cancer progression[1].
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