Physicochemical parameters vs. highest confirmed PTIP values of all test compounds used
Molecular properties were measured (LogD7.4, MDCK-LE Papp) or calculated (tPSA, cLogP, Kp,pred) as described in Materials and Methods. Highest PTIP values for each inhibitor are extracted from Table 2; where available, PTIP determined under “NSB block +” conditions was considered as confirmed. The respective transporter is noted in brackets. PTIP values ≥2.5x are highlighted in bold.
| Compound | Molecular Weight | tPSA | cLogP | LogD7.4 | MDCK-LE Papp | Kp, pred | Kp, pred/MDCK-LE Papp | Highest Confirmed PTIP |
|---|---|---|---|---|---|---|---|---|
| g/mol | Å | 10−6 cm/s | ||||||
| Abacavir | 286.3 | 104 | 1.2 | 1.2 | 12.6 | 16.4 | 1.30 | 0.892 (OCT1) |
| Amisulpride | 369.5 | 102 | 1.3 | −0.3 | 1.6 | 6.72 | 4.20 | 1.61 (OCT1) |
| Atorvastatin | 558.7 | 114 | 4.4 | 1.2 | 3.73 | 16.7 | 4.48 | 2.26 (OATP1B3) |
| Benzbromarone | 424.1 | 50.4 | 6 | 3.4 | 4.2 | 61.9 | 14.7 | 1.51 (OAT3) |
| Bumetanide | 364.4 | 119 | 3.4 | 0.03 | 1.13 | 8.4 | 7.43 | 1.32 (OAT3) |
| Cetirizine | 388.9 | 53 | 2.1 | 1.3 | 4.64 | 17.8 | 3.84 | 1.78 (OCT1) |
| Cimetidine | 252.3 | 88.9 | 0.3 | 0.3 | 1.5 | 9.63 | 6.42 | 1.71 (OCT1) |
| Cyclosporin A | 1202.6 | 279 | 14.0 | 4.0 | 3.71 | 87.7 | 23.6 | 6.78 (OATP1B1) |
| Daclatasvir | 738.9 | 174.6 | 4.7 | 4.5 | 3.72 | 116 | 31.2 | 34.2 (OCT2) |
| Diclofenac | 296.2 | 49.3 | 4.7 | 1.2 | 16.7 | 16.8 | 1.01 | 1.25 (OAT1) |
| Dolutegravir | 419.4 | 101 | −0.4 | 2.1 | 9.51 | 28.5 | 3.00 | 11.3 (OCT2) |
| Famotidine | 337.5 | 176 | −0.6 | −0.4 | 0.87 | 6.51 | 7.48 | 1.73 (MATE2-K) |
| Furosemide | 330.7 | 123 | 1.9 | −1.2 | 1.1 | 4.01 | 3.65 | 1.44 (OAT1) |
| Gemfibrozil | 250.3 | 46.5 | 3.9 | 2.1 | 12.3 | 28.5 | 2.32 | 1.21 (OAT3) |
| Irinotecan | 586.7 | 116.7 | 2.7 | 1.3 | 1.9 | 17.5 | 9.21 | 5.43 (OCT1) |
| Isavuconazole | 437.5 | 87.6 | 2.7 | 3.4 | 6.17 | 60.8 | 9.85 | 13.2 (OCT2) |
| Ledipasvir | 889 | 175 | 6.7 | >4.7 | 0.012 | 132.6 | 11,050 | >255 (OCT1) |
| Ondansetron | 293.4 | 44.8 | 2.1 | 1.6 | 16.9 | 21.2 | 1.25 | 1.57 (MATE1) |
| Pravastatin | 424.5 | 124 | 2.0 | −0.75 | 0.56 | 5.3 | 9.45 | — (OAT1)a |
| Probenecid | 285.4 | 74.7 | 3.4 | −0.7 | 7.31 | 5.45 | 0.75 | 1.58 (OAT3) |
| Pyrimethamine | 248.7 | 77.8 | 2.4 | 2.2 | 11.7 | 30.3 | 2.59 | 2.09 (MATE2-K) |
| Ranitidine | 314.4 | 86.3 | 0.7 | −0.6 | 1.3 | 5.7 | 4.38 | 0.668 (MATE1) |
| Ranolazine | 427.5 | 74.3 | 1.0 | 0.9 | 16.8 | 14.1 | 0.84 | 1.35 (OCT1) |
| Rifampicin | 823 | 220 | 1.5 | 1.1 | 1.44 | 16.3 | 11.3 | 1.72 (OATP1B3) |
| Saquinavir | 670.9 | 167 | 4.7 | 4.0 | 2.5 | 87.7 | 35.08 | 4.09 (OCT1) |
| Trimethoprim | 290.3 | 106 | 0.98 | 0.6 | 10.3 | 11.7 | 1.14 | 1.75 (MATE1) |
| Valsartan | 435.5 | 112 | 4.9 | −0.6 | 0.66 | 5.78 | 8.76 | 1.58 (OAT3) |
| Vandetanib | 475.4 | 59.5 | 3.7 | 2.6 | 8.45 | 39.4 | 4.66 | 4.19 (OCT2) |
| Venetoclax | 868.5 | 174.7 | 10.0 | >4.7 | 0.15 | 132.6 | 884.0 | >258 (OATP1B1) |
| Verapamil | 454.6 | 64 | 1.5 | 2.5 | 14.5 | 36.1 | 2.49 | 3.06 (OCT1) |
↵a PTIP of pravastatin is missing as IC50 values could not be determined.