Table 2.
Overview of small molecules used for cancer therapy as substrates of drug transporters
| Drug | Substrate of transporter | In vitro | Animal models |
|---|---|---|---|
| Dasatinib | P-glycoprotein (ABCB1) | CCRF-CEM cells (Hiwase et al., 2008), K562 cells (Hiwase et al., 2008; Hegedus et al., 2009; Haouala et al., 2010), MDCKII cells (Chen et al., 2009; Lagas et al., 2009) | Abcb1a/1b(–/–) mice (Lagas et al., 2009), Abcb1a/1b(–/–) Abcg2(–/–) mice (Chen et al., 2009; Lagas et al., 2009) |
| BCRP (ABCG2) | K562 cells (Hiwase et al., 2008; Hegedus et al., 2009), MDCKII cells (Chen et al., 2009; Lagas et al., 2009), murine fibroblast cell line MEF3.8 (Hiwase et al., 2008) | Abcb1a/1b(–/–) Abcg2(–/–) mice (Chen et al., 2009; Lagas et al., 2009) | |
| Erlotinib | OAT3 (SLC22A8) | HEK293 cells (Elmeliegy et al., 2011) | |
| OCT2 (SLC22A2) | HEK293 cells (Elmeliegy et al., 2011) | ||
| P-glycoprotein (ABCB1) | LLC-PK1 cells (Marchetti et al., 2008; Kodaira et al., 2010), MDCKII cells (Marchetti et al., 2008) | Abcb1a/1b(–/–) mice (Kodaira et al., 2010), Abcb1a/1b(–/–) Abcg2(–/–) mice (Marchetti et al., 2008; de Vries et al., 2010; Kodaira et al., 2010) | |
| BCRP (ABCG2) | HEK293 cells (Li et al., 2007), MDCKII cells (Marchetti et al., 2008; Kodaira et al., 2010), Saos2 cells (Elmeliegy et al., 2011) | Abcg2(–/–) mice (Kodaira et al., 2010; Elmeliegy et al., 2011), Abcb1a/1b(–/–) Abcg2(–/–) mice (Marchetti et al., 2008; de Vries et al., 2010; Kodaira et al., 2010; Elmeliegy et al., 2011) | |
| Gefitinib | P-glycoprotein (ABCB1) | MDCKII cells (Agarwal et al., 2010) | Abcb1a/1b(–/–) Abcg2(–/–) mice (Kawamura et al., 2009; Agarwal et al., 2010) |
| BCRP (ABCG2) | HEK293 cells (Li et al., 2007), MDCKII cells (Agarwal et al., 2010) | Abcb1a/1b(–/–) Abcg2(–/–) mice (Kawamura et al., 2009; Agarwal et al., 2010) | |
| Imatinib | OATP1A2 (SLC21A3) | HeLa cells (Eechoute et al., 2011a), Xenopus laevis oocytes (Hu et al., 2008; Yamakawa et al., 2011; Eechoute et al., 2011a) | |
| OATP1B3 (SLC21A8) | Xenopus laevis oocytes (Hu et al., 2008) | ||
| OCT1 (SLC22A1) | CEM cells (Thomas et al., 2004), CML cells (White et al., 2006), HEK293 cells (Hu et al., 2008), CML cells (Wang et al., 2008) | ||
| OCTN2 (SLC22A5) | HEK293 cells (Hu et al., 2008) | ||
| P-glycoprotein (ABCB1) | K562 cells (Mahon et al., 2003), LLC-PK1 cells (Hu et al., 2008), MDCKII cells (Dai et al., 2003; Thomas et al., 2004) | Abcb1a/1b(–/–) mice (Dai et al., 2003; Zhou et al., 2009), Abcb1a/1b(–/–) Abcg2(–/–) mice (Zhou et al., 2009) | |
| MRP4 (ABCC4) | Saos2 cells (Hu et al., 2008) | ||
| BCRP (ABCG2) | HEK293 cells (Burger et al., 2004), MCF7 cells (Burger et al., 2004), MDCKII cells (Breedveld et al., 2005), Saos2 cells (Hu et al., 2008) | Abcg2(–/–) mice (Zhou et al., 2009), Abcb1a/1b(–/–) Abcg2(–/–) mice (Zhou et al., 2009) | |
| Lapatinib | P-glycoprotein (ABCB1) | MDCKII cells (Polli et al., 2008) | Abcb1a/1b(–/–) mice (Polli et al., 2009), Abcb1a/1b(–/–) Abcg2(–/–) mice (Polli et al., 2009) |
| BCRP (ABCG2) | MDCKII cells (Polli et al., 2008) | Abcb1a/1b(–/–) Abcg2(–/–) mice (Polli et al., 2009) | |
| Nilotinib | P-glycoprotein (ABCB1) | K562 cells (Mahon et al., 2008) | |
| BCRP (ABCG2) | K562 cells (Hegedus et al., 2009) | ||
| Pazopanib | P-glycoprotein (ABCB1) | (FDA, 2010b) | |
| BCRP (ABCG2) | (FDA, 2010b) | ||
| Sorafenib | P-glycoprotein (ABCB1) | Human epithelial colorectal adenocarcinoma cells (Caco-2, Gnoth et al., 2010), K562 cells (Haouala et al., 2010), LLC-PK1 cells (Hu et al., 2009; Gnoth et al., 2010), MDCKII cells (Lagas et al., 2010) | Abcb1a/1b(–/–) mice (Hu et al., 2009; Gnoth et al., 2010), Abcb1a/1b(–/–) Abcg2(–/–) mice (Lagas et al., 2010; Asakawa et al., 2011) |
| MRP2 (ABCC2) | LLC-PK1 cells (Shibayama et al., 2011) | ||
| BCRP (ABCG2) | MDCKII cells (Lagas et al., 2010; Agarwal et al., 2011) | Abcg2(–/–) mice (Lagas et al., 2010; Agarwal et al., 2011), Abcb1a/1b(–/–) Abcg2(–/–) mice (Lagas et al., 2010; Agarwal et al., 2011; Asakawa et al., 2011) | |
| Sunitinib | P-glycoprotein (ABCB1) | K562 cells (Haouala et al., 2010), LLC-PK1 cells (Hu et al., 2009), MDCKII cells (Tang et al., 2011) | Abcb1a/1b(–/–) mice (Hu et al., 2009; Tang et al., 2011), Abcb1a/1b(–/–) Abcg2(–/–) mice (Tang et al., 2011) |
| BCRP (ABCG2) | MDCKII cellls (Tang et al., 2011) | Abcb1a/1b(–/–) Abcg2(–/–) mice (Tang et al., 2011) | |
| Everolimus | P-glycoprotein (ABCB1) | Caco-2 cells (Crowe and Lemaire, 1998) | Abcb1a/1b(–/–) mice (Chu et al., 2009) |
| Temsirolimus | P-glycoprotein (ABCB1) | Caco-2 cells (Crowe and Lemaire, 1998) | |
| Bortezomib | P-glycoprotein (ABCB1) | K562 cells (Rumpold et al., 2007) |
FDA, US Food and Drug Administration.