Ki16425
Ki16425 is a subtype-selective antagonist of lysophosphatidic acid receptor (LPA) with Ki values of 0.34 μM for LPA1, 6.5μM for LPA2, and 0.93μM for LPA3 [4].
It has been reported that Ki16425 inhibited the LPA receptor-mediated actions in the order of LPA1≥LPA3≥LPA2. Ki16425 inhibited LPA-induced guanosine 5’-O-(3-thio) triphosphate binding, membrane fractions binding, and was involved in the long-term responses, including DNA synthesis and cell migration [1]. Ki16425 attenuated LPA-mediated intracellular signaling and invasion responses in vitro. Co-treatment of Ki16425 and sunitinib prolonged the sensitivity of renal tumor cell to sunitinib in xenograft mouse models [3]. In human breast cancer cells, Ki16425 can inhibit heparin-binding EGF-like growth factor (HB-EGF) expression [4].
In mouse thoracic aorta, Ki16425 significantly reduced LPA-induced vasorelaxation [2]. Ki16425 treatment also blocked renal tumorigenesis in vivo [3]. A five-day treatment with Ki16425 significantly decreased both HB-EGF mRNA expression at the transplanted tumor site in mice and circulating human HB-EGF concentrations in serum [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]. Ruisanchez é, Dancs P, Kerék M, Németh T, Faragó B, Balogh A, Patil R, Jennings BL, Liliom K, Malik KU, Smrcka AV, Tigyi G, Benyó Z. Lysophosphatidic acid induces vasodilation mediated by LPA1 receptors, phospholipase C, and endothelial nitric oxide synthase. FASEB J. 2014 Feb;28(2):880-90.
[3]. Su SC, Hu X, Kenney PA, Merrill MM, Babaian KN, Zhang XY, Maity T, Yang SF, Lin X, Wood CG. Autotaxin-lysophosphatidic acid signaling axis mediates tumorigenesis and development of acquired resistance to sunitinib in renal cell carcinoma. Clin Cancer Res. 2013 Dec 1;19(23):6461-72.
[4]. David M, Sahay D, Mege F, Descotes F, Leblanc R, Ribeiro J, Clézardin P, Peyruchaud O. Identification of Heparin-Binding EGF-Like Growth Factor (HB-EGF) as a Biomarker for Lysophosphatidic Acid Receptor Type 1 (LPA1) Activation in Human Breast and Prostate Cancers. PLoS One. 2014 May 14;9(5):e97771.
- 1. Moreno-Fernández RD, Nieto-Quero A, et al. "Effects of genetic deletion versus pharmacological blockade of the LPA(1) receptor on depression-like behaviour and related brain functional activity." Dis Model Mech. 2018 Jul 30. pii: dmm.035519. PMID:30061118
- 2. Sánchez-Marín L, Ladrón de Guevara-Miranda D, et al. "Systemic blockade of LPA(1/3) lysophosphatidic acid receptors by ki16425 modulates the effects of ethanol on the brain and behavior." Neuropharmacology. 2018 May 1;133:189-201. PMID:29378212
- 3. Ladrón de Guevara-Miranda D, Moreno-Fernández RD, et al." Lysophosphatidic acid-induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine-contextual memory."Addict Biol. 2018 Feb 26. PMID:29480526
- 4. Loskutov YV, Griffin CL, et al. "LPA signaling is regulated through the primary cilium:a novel target in glioblastoma." Oncogene. 2018 Jan 11. PMID:29321663
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 474.96 |
| Cas No. | 355025-24-0 |
| Formula | C23H23ClN2O5S |
| Solubility | ≥23.75 mg/mL in DMSO; insoluble in H2O; ≥12.54 mg/mL in EtOH |
| Chemical Name | 3-[[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]methylsulfanyl]propanoic acid |
| SDF | Download SDF |
| Canonical SMILES | CC1=NOC(=C1NC(=O)OC(C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)CSCCC(=O)O |
| 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]: | |
|
Inositol phosphate production |
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 experiment [2]: | |
|
Cell lines |
MDA-MB-231 and PC3 cells |
|
Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reaction Conditions |
10 μM; 45 mins or 24 hrs |
|
Applications |
In human breast and prostate cancer cells, Ki16425 inhibited heparin-binding EGF-like growth factor (HB-EGF) expression. |
| Animal experiment [2]: | |
|
Animal models |
PC3 cell xenograft mouse model |
|
Dosage form |
25 mg/kg; s.c.; for 5 days |
|
Applications |
A five-day treatment with Ki16425 significantly decreased both HB-EGF mRNA expression at the transplanted tumor site in mice and circulating human HB-EGF concentrations in serum. |
|
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. |
|
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]. David M, Sahay D, Mege F, Descotes F, Leblanc R, Ribeiro J, Clézardin P, Peyruchaud O. Identification of Heparin-Binding EGF-Like Growth Factor (HB-EGF) as a Biomarker for Lysophosphatidic Acid Receptor Type 1 (LPA1) Activation in Human Breast and Prostate Cancers. PLoS One. 2014 May 14;9(5):e97771. |
|
| Description | Ki16425 is an antagonist of LPA receptor with Ki value of 0.34, 6.5 and 0.93 μM for human LPA1, LPA2 and LPA3 receptors, respectively. | |||||
| Targets | human LPA1 | human LPA2 | human LPA3 | |||
| IC50 | 0.34 μM | 6.5 μM | 0.93 μM | |||
Quality Control & MSDS
- View current batch:
Chemical structure
Related Biological Data
Related Biological Data
Related Biological Data
Related Biological Data
