Table 3.
Relative potencies (pIC50) of P2X7 antagonists at the rat, human and dog native and recombinant P2X7 orthologues
| Human ethidium | Dog ethidium | Rat ethidium | Human blood | Dog blood | |
|---|---|---|---|---|---|
| KN62 | 7.64 ± 0.10 | 7.98 ± 0.1 | <5* | 5.75 ± 0.10 | 6.76 ± 0.1 |
| GW791343 | 7.03 ± 0.02 | 6.70 ± 0.07 | Potentiate | <5 | ND |
| BBG | 6.49 ± 0.1 | 7.31 ± 0.07 | 6.8 ± 0.10* | <5 | <5 |
| Compound-17 | 8.58 ± 0.03 | 7.24 ± 0.03 | 7.55 ± 0.13 | 6.28 ± 0.08 | 5.63 ± 0.18 |
| GSK1271360 | 8.03 ± 0.08 | 7.31 ± 0.13 | 7.70 ± 0.10 | ND | ND |
| GSK314181 | 8.39 ± 0.02 | 7.31 ± 0.10 | 7.06 ± 0.02 | 6.39 ± 0.23 | 5.90 ± 0.03 |
| GSK361390 | 8.09 ± 0.06 | 7.43 ± 0.12 | 5.52 ± 0.03 | 5.99 ± 0.15 | 6.09 ± 0.35 |
Ethidium studies were performed in NaCl buffer at room temperature, and IL-1β release studies were in whole blood at 37°C using ATP as the agonist. Data are mean ± SEM, n= 3–4 experiments.
BBG, brilliant blue G; compound-17, N-[2-({2-[(2-hydroxyethyl)amino]ethyl}amino)-5-quinolinyl]-2-tricyclo[3.3.1.13,7]dec-1-ylacetamide; GSK1271360, 2-(1-adamantyl)-N-[2-({2-[bis(2 hydroxyethyl)amino]ethyl}amino)quinolin-5-yl]acetamide; GSK314181, 5-{[(3R)-3-amino-1-pyrrolidinyl]methyl}-2-chloro-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)benzamide; GSK361390, N-adamantan-1-ylmethyl-2-chloro-5-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-benzamide; GW791343, N2-(3,4-difluorophenyl)-N1-[2-methyl-5-(1-piperazinylmethyl)phenyl]glycinamide dihydrochloride; IL-1β, interleukin-1β; KN62, 1-(N,O-bis-[5-isoquinoline-sulphonyl]-N-methyl-L-tyroyl)-4-phenyl-piperazine; ND, not determined.
Data from Hibell et al. (2001).