Ki16198
Ki16198 is the methyl ester of Ki16425. Ki16198, a LPA antagonist, inhibits LPA1- and LPA3-induced inositol phosphate production with the Ki of 0.34 μM and 0.93 μM, respectively, shows weaker inhibition for LPA2, no activity at LPA4, LPA5, LPA6[1].
Lysophosphatidic acid (LPA) is an extracellular signaling lipid involved in regulating cell proliferation, survival, and motility of normal and cancer cells[2].
In vitro: In YAPC-PD cancer cell line, Ki16198 substantially inhibited LPA1- and LPA3-mediated responses with low potency to LPA2 and no activity to LPA4, LPA5 and LPA6. Treatment with Ki16198 (10 μM) effectively inhibited migration and invasion responses to LPA in YAPC-PD cancer cell line. Incubation of Ki16198 (10 μM) inhibited the LPA-induced expression of proMMP-9 protein and mRNA in YAPC-PD cells [1].Administration of Ki16198 (1 μM) inhibited the proliferation of lpa1Δ-1 and lpa1Δ+-1 cells by about 70% [2].
In vivo: In YAPC-PD pancreatic cancer cell-inoculated nude xenograft mouse model, Oral administration of Ki16198 (2 mg/kg) significantly inhibited tumor weight and remarkably attenuated invasion and metastasis to lung, liver, and brain and decreased the total metastatic node weight in the peritoneal cavity and ascites formation by 50% [1].Oral administration of Ki16198 (60 mg/kg) significantly inhibited lactate-induced limb lesions in rats [3].
References:
[1]. Komachi M, Sato K, Tobo M, et al. Orally active lysophosphatidic acid receptor antagonist attenuates pancreatic cancer invasion and metastasis in vivo[J]. Cancer science, 2012, 103(6): 1099-1104.
[2]. Shano S, Hatanaka K, Ninose S, et al. A lysophosphatidic acid receptor lacking the PDZ-binding domain is constitutively active and stimulates cell proliferation[J]. BiochimicaetBiophysicaActa (BBA)-Molecular Cell Research, 2008, 1783(5): 748-759.
[3]. Kimura T, Mogi C, Sato K, et al. p2y5/LPA6 attenuates LPA1-mediated VE-cadherin translocation and cell–cell dissociation through G12/13 protein–Src–Rap1[J]. Cardiovascular research, 2011: cvr154.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 488.98 |
| Cas No. | 355025-13-7 |
| Formula | C24H25ClN2O5S |
| Solubility | insoluble in H2O; ≥2.53 mg/mL in EtOH; ≥24.45 mg/mL in DMSO |
| Chemical Name | methyl 3-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]methylsulfanyl]propanoate |
| SDF | Download SDF |
| Canonical SMILES | CC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)CSCCC(=O)OC |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Kinase experiment [1]: | |
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Inositolphosphate response |
RH7777 cells expressing LPA1, LPA2, LPA3, LPA4, or LPA5 were cultured on collagen-coated 12-well dishes in the growth medium, and then the medium was changed to TCM199 containing 2 μCi/mL [3H]inositol and 0.1% (w/v) BSA (fraction V). After 24 hrs, the cells were washed 3 times with HEPES-buffered medium, which consisted of 20 mM Hepes (pH 7.4), 134 mM NaCl, 4.7 mM KCl, 1.2 mM KH2PO4, 1.2 mM MgSO4, 2 mM CaCl2, 2.5 mM NaHCO3, 5 mM glucose, and 0.1% (w/v) BSA, and incubated for 30 mins with the indicated concentrations of Ki16198 with or without 1 μM LPA in the presence of 10 mM LiCl in the same medium at final volume of 0.5 mL. The reaction was terminated by adding 1 N HCl (0.1 mL) and freezing the cells. The supernatant (acid extract in 0.5 mL) of the thawed cells was used for the separation of [3H]inositol phosphate fractions. The results were normalized to 105 dpm of the total radioactivity incorporated into the cellular inositol lipids. The radioactivity of the trichloroacetic acid (5%)-insoluble fraction was measured as the total radioactivity. |
| Cell experiment [1]: | |
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Cell lines |
YAPC-PD cells |
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Preparation method |
The solubility of this compound in DMSO is > 24.5 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
10 μM; 24 hrs |
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Applications |
In YAPC-PD cells, Ki16198 inhibited LPA-mediated migration and invasion. Moreover, Ki16198 inhibited LPA-induced expression of proMMP-9 protein and mRNA. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing YAPC-PD xenografts |
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Dosage form |
2 mg/kg; p.o. |
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Applications |
In mice bearing YAPC-PD xenografts, Ki16198 (2 mg/kg) substantially decreased the total metastatic node weight in the peritoneal cavity, as well as ascites formation by 50%. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Komachi M, Sato K, Tobo M, et al. Orally active lysophosphatidic acid receptor antagonist attenuates pancreatic cancer invasion and metastasis in vivo[J]. Cancer science, 2012, 103(6): 1099-1104. |
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Quality Control & MSDS
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Chemical structure
