Category I: concordance among in vitro Pgp assays
| Class | EAC Result | Number of Compounds | Mean Papp A → B | Median Papp A → B | Range of Papp A → B | Remarks |
|---|---|---|---|---|---|---|
| nm/s | ||||||
| Unambiguous nonsubstrates | NNN | 14 | 240 | 99.8 | 9.53–842 | 7/14 with Papp <20 nm/s 5/14 with Papp >300 nm/s Conclusions: nonsubstrates or possible combination of low assay responses and affinity for Pgp |
| Unambiguous substrates | YYY | 18 | 131 | 102 | 3.01–413 | 3/18 with Papp <20 nm/s 1/18 with Papp >300 nm/s Conclusions: optimal combination of assay responses and affinity for Pgp |
| Inhibitors | NNY | 3 | 559 | 758 | 2.12–916 | e.g., GF120918 |
n = 35 of 66 compounds. See Experimental Procedures for the details of each assay.
Definitions: EAC: E, monolayer efflux; A, drug-stimulated ATPase; C, calcein-AM. Results are reported as yes (Y) or no (N). For efflux, yes = substrate and no = nonsubstrate; for ATPase assays, yes = stimulator and no = no activity; and for calcein-AM assay, yes = response >10% maximum fluorescence and no = response <10% maximum fluorescence.