Ki-16425

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, respectively, shows no activity at LPA4, LPA5, LPA6. IC50 value: 0.3/6.5/0.93 uM(Ki, LPA1/2/3) Target: LPA1/2/3

Product information

CAS Number: 355025-24-0

Molecular Weight: 474.96

Formula: C23H23ClN2O5S

Chemical Name: 3-((4-(4-(((1-(2-chlorophenyl)ethoxy)carbonyl)amino)-3-methylisoxazol-5-yl)benzyl)thio)propanoic acid

Smiles: CC1=NOC(=C1NC(=O)OC(C)C1=CC=CC=C1Cl)C1C=CC(CSCCC(O)=O)=CC=1

InChiKey: LLIFMNUXGDHTRO-UHFFFAOYSA-N

InChi: InChI=1S/C23H23ClN2O5S/c1-14-21(25-23(29)30-15(2)18-5-3-4-6-19(18)24)22(31-26-14)17-9-7-16(8-10-17)13-32-12-11-20(27)28/h3-10,15H,11-13H2,1-2H3,(H,25,29)(H,27,28)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: 10 mM in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

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 .

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.

References:

1. Ohta H, et al. Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors.Mol Pharmacol, 2003, 64(4), 994-1005.
2. Moughal NA, et al. Protean agonism of the lysophosphatidic acid receptor-1 with Ki16425 reduces nerve growth factor-induced neurite outgrowth in pheochromocytoma 12 cells. J Neurochem, 2006, 98(6), 1920-1929.
3. Ma L, et al. Evidence for lysophosphatidic acid 1 receptor signaling in the early phase of neuropathic pain mechanisms in experiments using Ki-16425, a lysophosphatidic acid 1 receptor antagonist. J Neurochem, 2009, 109(2), 603-610.

Products are for research use only. Not for human use.