Stephanie van Hoppe

133 The impact of OATPs on disposition and toxicity of antitumor drugs; insights from KO and humanized mice Figure 2: Structures of anticancer drugs clearly affected by Oatp1a/1b activity in vivo . Drugs that are structurally closely related, but that are not appreciably affected by Oatp1a/1b-mediated transport in vivo are named in italics and marked with an asterisk. While paclitaxel and docetaxel are clearly transported, cabazitaxel, which differs in just two methoxy groups from docetaxel, is not appreciably transported by Oatp1a/1b in vivo . Oatp1a/1b activity in mice clearly affects disposition of both irinotecan and its active metabolite SN-38. Sorafenib itself is not noticeably transported by Oatp1a/1b in vivo , but its glucuronate conjugate sorafenib-β-D-glucuronide is. For cisplatin it should be noted that this drug is highly reactive, and only total Pt levels are measured in in vivo experiments. It is therefore possible that structurally different complexes resulting from cisplatin reactions are primarily transported by Oatp1a/1b proteins. Paclitaxel Docetaxel *Cabazitaxel Irinotecan SN-38 Cisplatin Sorafenib-β-D-Glucuronide *Sorafenib Methotrexate Doxorubicin Figure 2 - Struct res of anticancer s clearly affected by Oatp a/1b activity in vivo . Drugs that are structurally closely related, but that re not appreciably affected y Oatp1a/1b-mediated transport in vivo are named in italics and marked with an asterisk. While paclitaxel and docetaxel are clearly transported, cabazitaxel, which differs in just two methoxy groups from docetaxel, is not appreciably transported by Oatp1a/1b in vivo . Oatp1a/1b activity in mice clearly affects disposition of both irinotecan and its active metabolite SN-38. Sorafenib itself is not noticeably transported by Oatp1a/1b in vivo , but its glucuronate conjugate sorafenib-β-D-glucuronide is. For cisplatin it sh uld be noted that this drug is highly reactive, and only total Pt levels are measured in in vivo experiments. It is ther fore possible that structurally different complexes resulting from cisplatin reactions are primarily transported by Oatp1a/1b proteins.