The estimated contribution of toxicity to PTIP
To estimate fold IC50 change caused by the occasional toxicity of a test inhibitor, percent transport values measured without preincubation at each concentration of the compound were multiplied by percent viability values determined after a 3-h preincubation with the same concentration. Fold IC50 change owing to toxicity was either postulated to be 1.0 when the inhibitor did not impair viability by more than 10% even at the highest applied concentration, or estimated as (IC50 without toxicity)/(IC50 with toxicity). For more details please refer to the main text and Supplemental Fig.3.
| Inhibitor | Cell Line | A Fold IC50 Change owing to Preincubation (= PTIP) | B Fold IC50 Change owing to Toxicity (Estimated or *Postulated) | A/B Fold IC50 Change Corrected for Toxicity (Calculated) |
|---|---|---|---|---|
| Cyclosporin A | HEK-OATP1B1 | 6.78 | 1.0* | 6.78 |
| HEK-OATP1B3 | 3.02 | 1.0* | 3.02 | |
| Daclatasvir | HEK-OCT1 | 5.65 | 1.0* | 5.65 |
| HEK-OCT2 | 34.2 | 1.0* | 34.2 | |
| Dolutegravir | HEK-OCT2 | 11.3 | 1.0* | 11.3 |
| Irinotecan | HEK-OCT1 | 5.43 | 1.0* | 5.43 |
| Isavuconazole | HEK-OCT1 | 2.98 | 1.0* | 2.98 |
| HEK-OCT2 | 13.2 | 1.4 | 9.43 | |
| Ledipasvir | HEK-OCT1 | >255 | 1.0* | >255 |
| HEK-OCT2 | >8.73 | 1.0* | >8.73 | |
| Saquinavir | HEK-OATP1B1 | 3.54 | 1.0 | 3.54 |
| HEK-OATP1B3 | 3.78 | 0.91 | 4.15 | |
| HEK-OCT1 | 4.09 | 1.0* | 4.09 | |
| Vandetanib | HEK-OCT1 | 2.69 | 1.4 | 1.92 |
| HEK-OCT2 | 4.19 | 1.4 | 2.99 | |
| MDCKII-MATE2-K | 3.00 | 1.5 | 2.00 | |
| Venetoclax | HEK-OATP1B1 | >258 | 1.1 | >235 |
| HEK-OATP1B3 | >8.70 | 4.8 | >1.81 | |
| Verapamil | HEK-OCT1 | 3.06 | 1 | 3.06 |