product name Ki16425
Description: Ki16425 is a competitive, potent and reversible antagonist to LPA1, LPA2 and LPA3 with Ki of 0.34 μM, 6.5 μM and 0.93 μM in RH7777 cell lines, respectively, it shows selectivity for LPA1 and LPA3 and exhibits no activity at LPA4, LPA5, LPA6. Ki16425 reduces nerve growth factor-induced neurite outgrowth in pheochromocytoma 12 cells. ki16425 blunts abdominal and systemic inflammation in a mouse model of peritoneal sepsis.
References: Mol Pharmacol. 2003 Oct;64(4):994-1005; J Neurochem. 2006 Sep;98(6):1920-9; J Neurochem. 2009 Apr;109(2):603-10.
474.96
Formula
C23H23ClN2O5S
CAS No.
355025-24-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 94 mg/mL (197.9 mM)
Water: <1 mg/mL
Ethanol: 94 mg/mL (197.9 mM)
Solubility (In vivo)
5% DMSO+95% Corn oil: 30 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: Kil6425 preferentially inhibits LPA1- and LPA3-mediated responses but has only a moderate effect on LPA2. Ki16425 inhibits the LPA-induced Ca(2+) response in THP-1 cells, 3T3 fibroblasts, and A431 cells, but had only a marginal effect in PC-12 cells and HL-60 cells, which means that Ki16425 seems to be a useful tool for evaluating the involvement of specific LPA receptors in the short-term response to LPA. Ki16425 inhibits long-term DNA synthesis and cell migration as induced by LPA in Swiss 3T3 fibroblasts. Ki16425 reduces the LPA-induced activation of p42/p44 mitogen activated protein kinase (MAPK), while acting as a weak stimulator of p42/p44 MAPK on its own, properties typical of a protean agonist. Ki16425 also significantly reduces the NGF-induced stimulation of p42/p44 MAPK and inhibited NGF-stimulated neurite outgrowth in PC-12 cells. Ki16425 markedly inhibits the expressions of COX-2 protein induced by synovial fluids. The enhancement of the IL-1 action by LPA on COX-2 expression is also inhibited by Ki16425. Kinase Assay: RH7777 cells are incubated for 1 min with or without Ki16425, and the inositol phosphates (sum of inositol bisphosphate and inositol trisphosphate) were measured. The results were normalized to 105 dpm of the total radioactivity incorporated into the cellular inositol lipids, and the radioactivity of trichloroacetic acid (5%)-insoluble fraction was considered as the total radioactivity. Cell Assay: In human breast and prostate cancer cells, Ki16425 inhibited heparin-binding EGF-like growth factor (HB-EGF) expression. |
|---|---|
| In Vivo | Ki-16425 (30 mg/kg, i.p.) completely blocks LPA-induced neuropathic pain-like behaviors, when administered 30 min but not 90 min before lysophosphatidic acid injection, suggesting that Ki-16425 is a short-lived inhibitor. Ki-16425 also inhibits nerve injury-induced up-regulation of Caα2δ-1 in the dorsal root ganglion and reduction of SP immunoreactivity in the spinal dorsal horn. |
| Animal model | Male standard ddY-strain mice |
| Formulation & Dosage | Dissolved in sesame oil; 30 mg/kg; i.p. administration. |
| References | Mol Pharmacol. 2003 Oct;64(4):994-1005; J Neurochem. 2006 Sep;98(6):1920-9; J Neurochem. 2009 Apr;109(2):603-10. |
