PF-04457845
| Target | FAAH |
| Targeted domain | Active site (covalent binding to Ser241) |
| Mode of action | Covalent inhibitor |
| Control | PF-04875474 |
| Recommended cellular usage concentration | 0.2 - 1 µM |
| In vivo use | yes |
| Donated by | Pfizer |
Probe criteria
| Inhibitor/agonist potency: goal is < 100 nM (IC50, Kd) | IC50 = 7.2 nM ± 0.63 (following 60 min pre-incubation) |
| Selectivity within target family: > 30-fold | Exquisite selectivity for FAAH relative to other mammalian serine hydrolases (tested 200 serine hydrolases at 10 and 100 µM). |
| Selectivity outside target family | CEREP panel screen with 68 targets at 10 µM: Closest off-target is HTR2A (Ki = 1.6 µM)In human and mouse membrane proteomes no off-targets were observed at the top dose of 100 µM. Shows off-target activity in the PDSP scan: Closest hits are HTR2A (Ki = 248.71 nM) and TMEM97 (Sigma2) (Ki = 436.72 nM). |
| On target cell activity for cell-based targets: goal is < 1 µM IC50/EC50 | PF-04457845 completely inhibited FAAH in human and mouse membrane proteomes at both 10 and 100 μM. |
| Control compound (100 times less potent than the probe) | Binding IC50 = >100 μM;One hit in the PDSP scan: TMEM97 (Ki = 8412.01 nM). |