Biological Activity
Gefapixant (AF-219, MK-7264) is a P2X3 antagonist for ATP-gated ion-channel and sensory signaling research. Gefapixant (AF-219) acts at a pocket involving the left-flipper and lower-body domains rather than the ATP orthosteric site.
In Vitro
| Endpoint | Model / conditions / source | Reported result |
|---|---|---|
| Allosteric mechanism | P2X3 receptor structural and functional study. [1] | Gefapixant (AF-219) acts at a pocket involving the left-flipper and lower-body domains rather than the ATP orthosteric site. |
| Species-dependent response | Chicken P2X3 wild type and A196G variant; rat G189A variant; AF-219 30 µM with ATP 10 µM. [1] | Wild-type chicken P2X3 was not inhibited at 30 µM; residue substitutions altered antagonist sensitivity. |
| Receptor discrimination | P2X2/P2X3 chimeras and mutational analysis. [1] | The experiments connected pocket geometry to P2X3 antagonist sensitivity. |
In Vivo
No compound-specific animal efficacy result is established by the sources summarized here.
Compound and Evidence Context
| Endpoint | Model / conditions / source | Reported result |
|---|---|---|
| Potency interpretation | Gefapixant versus AF-353 and receptor variants. [1] | AF-353 measurements and mutant/species-specific responses are not presented as human wild-type gefapixant IC50 values. |
Interpretation
Receptor selectivity in this study does not imply absence of effects on heteromeric P2X2/3 channels or taste-related adverse effects.
