Table 1 Commonly used P2 × 7R antagonists/(IC50)
From: Role of the P2 × 7 receptor in neurodegenerative diseases and its pharmacological properties
Antagonists | Chemical formula | Weight | Species | Antagonistic activity | Ref |
|---|---|---|---|---|---|
Brilliant Blue G(BBG) | C47H48N3NaO7S2 | 854.02 | Rat IC50 = 10.1 nM Human IC50 = 265 nM | It is a selective antagonist, but restrictedby its poor stability and less desirable pharmacokinetics properties, preventing their use for in vivo studies of the receptoruse for in vivo studies of the receptor | [61] |
JNJ-54,175,446 | C18H13ClF4N6O | 440.78 | Human IC50 = 8.46 nM Rat IC50 = 8.81 nM Mouse IC50 = 7.8 nM | A potent P2 × 7 antagonist with significant brain penetration and exhibiting dose-dependent P2 × 7 receptor occupancy in the hippocampus of rats and dogs, it has been shown to attenuate dexamphetamine-induced psychomotor hyperactivity and cognitive effects | [62] |
JNJ-55,308,942 | C17H12F5N7O | 425.323 | Human IC50 = 10 nM Rat IC50 = 15 nM | JNJ-55,308,942 is orally bioavailable, treatment with JNJ-55,308,942 (30 mg/kg; p.o.) attenuates LPS-induced microglial activation in mice | [54] |
A-804,598 | C19H17N5 | 315.372 | Human IC50 = 10.9 nM Rat IC50 = 9.9 nM Mouse IC50 = 8.9 nM | In differentiated THP-1 cells that expressed human P2 × 7 receptors, A-804,598 inhibited BzATP stimulated Yo-Pro uptake and release of IL-1β. In 1321N1 cells expressed recombinant rat P2 × 7 receptor, A 804,598 showed high affinity with Kd = 2.4 nM | |
SMW139 [11 C]SMW139 | C19H21ClF3NO2 C1811CH21ClF3NO2 | 386.824 | Mouse IC50 = 24 ± 5.5 nM Human IC50 = 158 ± 44 nM | It has a high affinity for P2 × 7R(Kd = 20.6 ± 1.7 nM), good in vivo stability and the ability to cross the blood-brain barrier, and PET tracers based on it are thought to be useful for detecting the exact role of microglia in CNS disease processes and their activation status | |
[11 C]JNJ-54,173,717 | Human IC50 = 4.2 ± 0.01 nM Rat IC50 = 7.6 ± 0.01 nM | ||||
JNJ-47,965,567 | C28H32N4O2 | 488.6 | Human IC50 = 8.3 nM Macaque IC50 = 8.6 nM Dog IC50 = 8.5 nM Rat IC50 = 7.2 nM Mouse IC50 = 7.5 nM | Treatment with the P2 × 7R antagonist JNJ47965567 delayed disease onset, reduced body weight loss and improved motor coordination and phenotypic score in female SOD1G93A mice |