Table 3.
Overview of small molecules used for cancer therapy as inhibitors of drug transporters
| Drug | Inhibition of transporter | Substrate | In vitro/animal model |
|---|---|---|---|
| Dasatinib | P-glycoprotein (ABCB1) | Calcein-AM | K562 cells (Hegedus et al., 2009) |
| BCRP (ABCG2) | Hoechst 33342 | K562 cells (Hegedus et al., 2009) | |
| Erlotinib | OCT1 (SLC22A1) | Metformin (IC50 = 0.356 µM) | HEK293 cells (Minematsu and Giacomini, 2011) |
| MATE2-K (SLC47A2) | Metformin (IC50 = 3.45 µM) | HEK293 cells (Minematsu and Giacomini, 2011) | |
| P-glycoprotein (ABCB1) | Vincristine (IC50 = 2 µM) | K562 cells (Noguchi et al., 2009) | |
| MRP7 (ABCC10) | Paclitaxel | HEK293 cells (Kuang et al., 2010) | |
| BCRP (ABCG2) | E217βG, methotrexate, mitoxantrone | HEK293 (Shi et al., 2007), K562 cells (Noguchi et al., 2009) | |
| Gefitinib | OCT1 (SLC22A1) | MPP+ | HEK293 cells (Galetti et al., 2010) |
| OCT2 (SLC22A2) | MPP+ | HEK293 cells (Galetti et al., 2010) | |
| MATE2-K (SLC47A2) | Metformin (IC50 = 0.194 µM) | HEK293 cells (Minematsu and Giacomini, 2011) | |
| P-glycoprotein (ABCB1) | Calcein-AM, docetaxel, doxorubicin, paclitaxel, rhodamine-123, topotecan | CL1 cells (Yang et al., 2005), LLC-PK1 cells (Leggas et al., 2006), MCF7 cells (Kitazaki et al., 2005; Yang et al., 2005), human small cell lung cancer cell line PC-6 (Kitazaki et al., 2005) | |
| BCRP (ABCG2) | Hoechst 33342, estrone-3-sulfate (IC50 = 1.0 µM), mitoxantrone, topotecan (Ki = 1.0 µM) | CL1 cells (Yang et al., 2005), HL60 cells (Ozvegy-Laczka et al., 2004), K562 cells (Yanase et al., 2004), MCF7 cells (Yang et al., 2005), PC-6 cells (Nakamura et al., 2005), Saos2 cells (Leggas et al., 2006) | |
| Imatinib | OCT1 (SLC22A1) | Metformin (IC50 = 1.47 µM) | HEK293 cells (Minematsu and Giacomini, 2011) |
| MATE1 (SLC47A1) | Metformin (IC50 = 0.048 µM) | HEK293 cells (Minematsu and Giacomini, 2011) | |
| MATE2-K (SLC47A2) | Metformin (IC50 = 0.478 µM) | HEK293 cells (Minematsu and Giacomini, 2011) | |
| P-glycoprotein (ABCB1) | Calcein-AM (Ki = 18.3 µM) | LLC-PK1 cells (Hamada et al., 2003) | |
| MRP7 (ABCC10) | Paclitaxel | HEK293 cells (Shen et al., 2009) | |
| BCRP (ABCG2) | Mitoxantrone, SN-38, topotecan | HEK293 cells (Burger et al., 2004), MCF7 cells (Burger et al., 2004), Saos2 cells (Houghton et al., 2004) | |
| Lapatinib | OATP1B1 (SLCO21A6) | E217βG | CHO cells (Polli et al., 2008; Fachinformation, 2010) |
| P-glycoprotein (ABCB1) | Topotecan | CHO cells (Molina et al., 2008) | |
| MRP7 (ABCC10) | Paclitaxel | HEK293 cells (Kuang et al., 2010) | |
| BCRP (ABCG2) | E217βG, methotrexate, SN-38, topotecan | HEK293 cells (Dai et al., 2008), H1975 cells (Perry et al., 2010), H358 cells (Perry et al., 2010), MDA-MB-231 cells (Molina et al., 2008; Perry et al., 2010), Susa S/R cells (Perry et al., 2010) | |
| Nilotinib | OCT1 (SLC22A1) | Metformin | CML cells (Davies et al., 2009), HEK293 cells (Minematsu and Giacomini, 2011) |
| OCT3 (SLC22A3) | Metformin (IC50 = 0.35 µM) | HEK293 cells (Minematsu and Giacomini, 2011) | |
| P-glycoprotein (ABCB1) | Calcein-AM, dasatinib, rhodamine | CML cells (Davies et al., 2009; Hiwase et al., 2010), HEK293 cells (Dohse et al., 2010), K562 cells (Hegedus et al., 2009) | |
| MRP7 (ABCC10) | Paclitaxel | HEK293 cells (Shen et al., 2009) | |
| BCRP (ABCG2) | E217βG, Hoechst 33342, methotrexate (Ki = 0.69 µM), pheophorbide A | CML cells (Davies et al., 2009), HEK293 cells (Tiwari et al., 2009; Dohse et al., 2010), HSC cells (Brendel et al., 2007), K562 cells (Hegedus et al., 2009) | |
| Pazopanib | OATP1B1 (SLC21A6) | (FDA, 2010b; Keisner and Shah, 2011) | |
| P-glycoprotein (ABCB1) | (FDA, 2010b) | ||
| BCRP (ABCG2) | (FDA, 2010b) | ||
| Sorafenib | P-glycoprotein (ABCB1) | Calcein-AM, vinblastine | LLC-PK1 (Hu et al., 2009), MDCKII cells (Agarwal et al., 2011) |
| MRP2 (ABCC2) | Docetaxel | Saos2 cells (Hu et al., 2009) | |
| MRP4 (ABCC4) | PMEA | Saos2 cells (Hu et al., 2009) | |
| BCRP (ABCG2) | Hoechst 33342 | Saos2 cells (Hu et al., 2009) | |
| Sunitinib | P-glycoprotein (ABCB1) | Calcein-AM, rhodamine 123, vincristine (Ki = 7.6 µM) | HEK293 cells (Shukla et al., 2009), K562 cells (Kawahara et al., 2010), LLC-PK1 cells (Hu et al., 2009) |
| MRP2 (ABCC2) | Docetaxel | Saos2 cells (Hu et al., 2009) | |
| MRP4 (ABCC4) | PMEA | Saos2 cells (Hu et al., 2009) | |
| BCRP (ABCG2) | Estrone-3-sulfate (Ki = 0.32 µM), Hoechst 33342, methotrexate, pheophorbide A, rhodamine 123 | HEK293 cells (Dai et al., 2009; Shukla et al., 2009), K562 cells (Kawahara et al., 2010), Saos2 cells (Hu et al., 2009), S1-M1-80 cells (Dai et al., 2009) | |
| Everolimus | OATP1A2 (SLC21A3) | Estrone-3-sulfate (IC50 = 4.2 µM) | Picard et al., 2011 |
| OATP1B1 (SLC21A6) | Estrone-3-sulfate (IC50 = 4.1 µM) | Picard et al., 2011 | |
| OATP1B3 (SLC21A8) | Mycophenolic acid 7-O-glucuronide (IC50 = 4.3 µM) | Picard et al., 2011 | |
| Temsirolimus | OATP1A2 (SLC21A3) | Estrone-3-sulfate (IC50 = 11.9 µM) | Picard et al., 2011 |
| OATP1B1 (SLC21A6) | Estrone-3-sulfate (IC50 = 9.8 µM) | Picard et al., 2011 | |
| OATP1B3 (SLC21A8) | Mycophenolic acid 7-O-glucuronide (IC50 = 1.3 µM) | Picard et al., 2011 | |
| P-glycoprotein (ABCB1) | Fachinformation, 2011 | ||
| Bortezomib | NC | NC | NC |
FDA, US Food and Drug Administration; NC, not characterized in humans.