Eosinophils adhesion assay as a tool for phenotypic drug screening - The pharmacology of 1,3,5 – Triazine and 1H-indole like derivatives against the human histamine H4 receptor
1H-indole like derivative
Male
0301 basic medicine
Cell Membrane Permeability
Indoles
TR-AF-45 (4-(4-methylpiperazin-1-yl)-6-neopentyl-1,3,5-triazin-2-amine)
KP-9D (2-(4-chlorophenyl)-4-(4-methylpiperazin-1-yl)-1,3,5-triazine)
Cell Survival
Croton Oil
JNJ10191584 (5-chloro-1H-benzo[d]imidazol-2-yl)(4-methylpiperazin-1-yl)methanone) Pub- Chem CID: 10446295)
Anti-Inflammatory Agents
Drug Evaluation, Preclinical
610
TR-AF-49 (4-(cyclohexylmethyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine)
Eosinophil
Mice
03 medical and health sciences
TR-7 (4-(4-chlorophenyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine)
615
Cell Line, Tumor
Drug Discovery
Cell Adhesion
Animals
Edema
Humans
Computer Simulation
Endothelium
JN-35 (4-(4-methylpiperazin-1-yl)-6-(3-phenylpropyl)-1,3,5-triazin-2-amine)
Histamine receptor
JNJ7777120 (5-chloro-1H-indol-2-yl)(4-methylpiperazin-1-yl)methanone) Pub- Chem CID: 4908365)
Cell Line, Transformed
0303 health sciences
Pruritus
Endothelial Cells
3. Good health
Eosinophils
Disease Models, Animal
1,3,5 – Triazine derivative
Adhesion
TR-DL-20 (4-(1-cyclohexenylmethyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine)
JN-25 (4-[(E)-2-(3-chlorophenyl)ethenyl]-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine)
TR-18 (4-(4-bromophenyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine)
MWJ-3 (5-chloro-7-nitro-1H-indol-2-yl)(4-methylpiperazin-1-yl)methanone Pub- Chem CID: 70692530)
Histamine
DOI:
10.1016/j.ejphar.2020.173611
Publication Date:
2020-10-02T06:53:41Z
AUTHORS (12)
ABSTRACT
Histamine is a pleiotropic biogenic amine, having affinity towards four distinct histamine receptors. The existing pharmacological studies suggest the usefulness of histamine H4 receptor ligands in the treatment of many inflammatory and immunomodulatory diseases, including allergic rhinitis, asthma, atopic dermatitis, colitis or pruritus. Up to date, several potent histamine H4 receptor ligands were developed, none of which was registered as a drug yet. In this study, a series of potent indole-like and triazine derivatives were tested, in radioligand displacement and functional assays at histamine H4 receptor, as well as in human eosinophils adhesion assay to endothelium. For selected compounds permeability, cytotoxicity, metabolic and in vivo studies were conducted. Adhesion assay differentiated the activity of different groups of compounds with a known affinity towards the histamine H4 receptor. Most of the tested compounds downregulated the number of adherent cells. However, adhesion assay revealed additional properties of tested compounds that had not been detected in radioligand displacement and aequorin-based functional assays. Furthermore, for some tested compounds, these abnormal effects were confirmed during the in vivo studies. In conclusion, eosinophils adhesion assay uncovered pharmacological activity of histamine H4 receptor ligands that has been later confirmed in vivo, underscoring the value of well-suited cell-based phenotypic screening approach in drug discovery.
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CITATIONS (6)
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