TABLE 2.
Drug glucuronides (-G and -AG) and sulfates (-S) studied as inhibitors in transporter overexpression systems.
| Drug conjugate | Inhibited uptake transporter a | Inhibited efflux transporter a | References |
|---|---|---|---|
| Abiraterone-N-oxide-S | OAT3 (Ki = 1 µM) | Zou et al. (2021) | |
| OAT1 (-) | |||
| Abiraterone-S | OAT1 (Ki = 38 µM) | Zou et al. (2021) | |
| OAT3 (Ki = 2 µM) | |||
| Brexanolone-S | NTCP (Ki = 8 µM) | Abu-Hayyeh et al. (2010) | |
| Cabozantinib M2a (sulfate) | OAT1 (IC50 = 4 µM) | BSEP (IC50 = 50 µM) | Lacy et al. (2015) |
| OAT3 (IC50 = 4 µM) | MATE1 (IC50 = 17 µM) | ||
| OATP1B1 (IC50 = 6 µM) | MATE2K (IC50 = 65 µM) | ||
| OATP1B3 (IC50 = 21 µM) | MRP2 (IC50 = 79 µM) | ||
| OCT1 (-) | P-gp (-) | ||
| OCT2 (-) | |||
| Clopidogrel-AG | OATP1B1 (IC50 = 11-51 µM) | Tamraz et al. (2013); Shebley et al. (2017) | |
| Diclofenac-AG | OAT1 (IC50 = 265 µM) | BCRP (20% at 100 µM) | Nozaki et al. (2007); Kawase et al. (2016); Iwaki et al. (2017) |
| OAT3 (IC50 = 3 µM) | MRP2 (IC50 = 19 µM) | ||
| MRP4 (IC50 = 140 µM) | |||
| Epacadostat-G | OATP1B1 (IC50 = 262 µM) | BCRP (-) | Zhang et al. (2017) |
| OATP1B3 (IC50 = 27 µM) | P-gp (-) | ||
| OAT1 (-) | |||
| OAT3 (-)OCT2 (-) | |||
| Ezetimibe-G | OATP1B1 (IC50 = 0.2 µM) | BCRP (IC50 = 52 µM) | Oswald et al. (2006); Oswald et al. (2008); de Waart et al. (2009) |
| OATP1B3 (IC50 = 0.3 µM) | MRP2 (IC50 = 34 µM) | ||
| OATP2B1 (IC50 = 0.1 µM) | MRP3 (IC50 = 7 µM) | ||
| P-gp (60% at 100 µM) | |||
| Fasiglifam-AG | OATP1B1 (IC50 = 1 µM) | BSEP (IC50 = 33 µM) | Otieno et al. (2018); Ackerson et al. (2019) |
| OATP1B3 (IC50 = 1 µM) | MRP2 (IC50 = 1 µM) | ||
| MRP3 (IC50 = 0.2 µM) | |||
| MRP4 (IC50 = 0.9 µM) | |||
| Fevipiprant-AG | OAT3 (Ki = 16 µM) | Poller et al. (2019) | |
| OATP1B1 (Ki = 31 µM) | |||
| OATP1B3 (Ki = 12 µM) | |||
| OAT1 (-) | |||
| (R)-Flurbiprofen-AG | OAT1 (IC50 =198 µM) | MRP2 (IC50 = 30 µM) | Kawase et al. (2016); Iwaki et al. (2017) |
| OAT3 (IC50 = 19 µM) | MRP4 (IC50 = 3 µM) | ||
| (S)-Flurbiprofen -AG | OAT1 (IC50 = 174 µM) | MRP2 (IC50 = 22 µM) | Kawase et al. (2016); Iwaki et al. (2017) |
| OAT3 (IC50 = 32 µM) | MRP4 (IC50 = 93 µM) | ||
| Gemfibrozil-AG | OAT3 (IC50 = 20 µM) | Hirano et al. (2006); Nakagomi-Hagihara et al. (2007a, 2007b) | |
| OATP1B1 (Ki = 8-23 µM) | |||
| (R)-Ibuprofen -AG | OAT1 (IC50 = 791 µM) | MRP2 (IC50 = 208 µM) | Kawase et al. (2016); Iwaki et al. (2017) |
| OAT3 (IC50 = 60 µM) | MRP4 (IC50 = 4 µM) | ||
| (S)-Ibuprofen-AG | OAT1 (IC50 = 960 µM) | MRP2 (IC50 = 81 µM) | Kawase et al. (2016); Iwaki et al. (2017) |
| OAT3 (IC50 = 57 µM) | MRP4 (IC50 = 67 µM) | ||
| (S)-Ketoprofen-AG | OAT1 (Ki = 40 µM) | Zou et al. (2021) | |
| OAT3 (Ki = 8 µM) | |||
| Micafungin (sulfate) | BCRP (IC50 = 21 µM) | Lempers et al. (2016) | |
| BSEP (IC50 = 85 µM) | |||
| MRP1 (IC50 = 21 µM) | |||
| MRP2 (IC50 = 148 µM) | |||
| MRP3 (IC50 = 42 µM) | |||
| MRP4 (IC50 = 4 µM) | |||
| MRP5 (IC50 = 22 µM) | |||
| P-gp (IC50 = 45 µM) | |||
| MK-8666-AG | BSEP (28% at 25 µM) | Hafey et al. (2020) | |
| Mycophenolic acid-AG | OAT1 (13% at 100 µM) | Wolff et al. (2007) | |
| OAT3 (IC50 = 3 µM) | |||
| Mycophenolic acid phenyl-G (MPA-G) | OAT1 (IC50 = 223-512 µM) | MRP2 (IC50 = 1037 µM) | Takekuma et al. (2007); Uwai et al. (2007); Wolff et al. (2007) |
| OAT3 (IC50 = 15-69 µM) | |||
| (R)-Naproxen-AG | OAT1 (IC50 = 639 µM) | MRP2 (IC50 = 771 µM) | Kawase et al. (2016); Iwaki et al. (2017) |
| OAT3 (IC50 = 129 µM) | MRP4 (IC50 = 2 µM) | ||
| (S)-Naproxen-AG | OAT1 (IC50 = 747 µM) | BCRP (20% stimulation at 100 µM) | Nozaki et al. (2007); Kawase et al. (2016); Iwaki et al. (2017); Zou et al. (2021) |
| OAT3 (Ki = 5 µM) | MRP2 (IC50 = 475 µM) | ||
| MRP4 (IC50 = 49 µM) | |||
| Probenecid-AG | OAT1 (Ki = 130 µM) | Zou et al. (2021) | |
| OAT3 (Ki = 20 µM) | |||
| Raloxifene-4′-G | OATP1B1 (65% at 10 µM) OATP1B3 (100% at 10 µM) | BCRP (IC50 = 0.3 µM) | Trdan Lušin et al. (2012a); Trdan Lušin et al. (2012b) |
| MRP1 (IC50 = 4 µM) | |||
| MRP2 (IC50 = 2 µM) | |||
| MRP3 (IC50 = 8 µM) | |||
| P-gp (IC50 = 6 µM) | |||
| BSEP (-) | |||
| Raloxifene-6,4′-diG | OATP1B1 (54% at 4 µM) OATP1B3 (100% at 4 µM) | BCRP (IC50 = 3 µM) | Trdan Lušin et al. (2012a); Trdan Lušin et al. (2012b) |
| MRP1 (IC50 = 2 µM) | |||
| MRP2 (50% at 4 µM) | |||
| MRP3 (IC50 = 0.5 µM) | |||
| P-gp (IC50 = 0.8 µM) | |||
| BSEP (-) | |||
| Raloxifene-6-G | OATP1B1 (-) | BCRP (IC50 = 40 µM) | Trdan Lušin et al. (2012a); Trdan Lušin et al. (2012b) |
| OATP1B3 (-) | MRP1 (IC50 = 1 µM) | ||
| MRP3 (IC50 = 10 µM) | |||
| P-gp (IC50 = 10 µM) | |||
| BSEP (-) | |||
| MRP2 (-) | |||
| Relebactam (sulfate) | OAT1 (-) | BSEP (12% at 500 µM) | Chan et al. (2019) |
| OAT3 (-) | P-gp (16% at 300 µM) | ||
| OATP1B1 (-) | BCRP (-) | ||
| OATP1B3 (-) | MATE1 (-) | ||
| OCT2 (-) | MATE2K (-) | ||
| Rosiglitazone-5-hydroxy-S | OAT1 (Ki = 34 µM) | Zou et al. (2021) | |
| OAT3 (Ki = 1 µM) | |||
| SN-38-G | OATP1B1 (13% at 10 µM) | Nozawa et al. (2005) | |
| Thyroxine-G | OATP2B1 (IC50 = 45 µM) | Meyer Zu Schwabedissen et al. (2018) | |
| Tolmetin-AG | OAT1 (Ki = 7 µM) | Zou et al. (2021) | |
| OAT3 (Ki = 3 µM) | |||
| Troglitazone-G | OATP1B1 (69% at 10 µM) | Nozawa et al. (2004) | |
| OATP1B3 (12% at 10 µM) | |||
| Troglitazone-S | OATP1B1 (95% at 10 µM) | MRP4 (Ki = 8 µM) | Nozawa et al. (2004); Yang et al. (2015); Malinen et al. (2019) |
| OATP1B3 (83% at 10 µM) | |||
| OSTα/β (IC50 = 191 µM) | |||
| Vericiguat-G | OATP1B1 (IC50 = 26 µM) | MATE1 (-) | Boettcher et al. (2020) |
| OATP1B3 (IC50 = 17 µM) | MATE2K (-) | ||
| P-gp (-) |
a
Inhibition reported as inhibitory constant (Ki), half-maximal inhibitory concentration (IC50) or inhibition percentage at a defined concentration of the inhibitor. (-) denotes transporters that have been shown not to be inhibited.