The SLCO superfamily is comprised of the organic anion transporting polypeptides (OATPs). The 11 human OATPs are divided into 6 families and ten subfamilies based on amino acid identity. These proteins are located on the plasma membrane of cells throughout the body. They have 12 TM domains and intracellular termini, with multiple putative glycosylation sites. OATPs mediate the sodium-independent uptake of a wide range of amphiphilic substrates, including many drugs and toxins. Due to the multispecificity of these proteins, this guide lists classes of substrates and inhibitors for each family member. More comprehensive lists of substrates, inhibitors, and their relative affinities may be found in the review articles listed below.

* Key recommended reading is highlighted with an asterisk

Gong IY, Kim RB. (2013) Impact of genetic variation in OATP transporters to drug disposition and response. Drug Metab Pharmacokinet, 28 (1): 4-18. [PMID:23047721]

Hagenbuch B. (2010) Drug uptake systems in liver and kidney: a historic perspective. Clin Pharmacol Ther, 87 (1): 39-47. [PMID:19924123]

* Hagenbuch B, Stieger B. (2013) The SLCO (former SLC21) superfamily of transporters. Mol Aspects Med, 34 (2-3): 396-412. [PMID:23506880]

* Hillgren KM, Keppler D, Zur AA, Giacomini KM, Stieger B, Cass CE, Zhang L, International Transporter Consortium. (2013) Emerging transporters of clinical importance: an update from the International Transporter Consortium. Clin Pharmacol Ther, 94 (1): 52-63. [PMID:23588305]

* International Transporter Consortium, Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, Chu X, Dahlin A, Evers R, Fischer V et al.. (2010) Membrane transporters in drug development. Nat Rev Drug Discov, 9 (3): 215-36. [PMID:20190787]

Keppler D. (2014) The roles of MRP2, MRP3, OATP1B1, and OATP1B3 in conjugated hyperbilirubinemia. Drug Metab Dispos, 42 (4): 561-5. [PMID:24459177]

König J. (2011) Uptake transporters of the human OATP family: molecular characteristics, substrates, their role in drug-drug interactions, and functional consequences of polymorphisms. Handb Exp Pharmacol, (201): 1-28. [PMID:21103967]

König J, Müller F, Fromm MF. (2013) Transporters and drug-drug interactions: important determinants of drug disposition and effects. Pharmacol Rev, 65 (3): 944-66. [PMID:23686349]

* Lee HH, Ho RH. (2017) Interindividual and interethnic variability in drug disposition: polymorphisms in organic anion transporting polypeptide 1B1 (OATP1B1; SLCO1B1). Br J Clin Pharmacol, 83 (6): 1176-1184. [PMID:27936281]

Murray M, Zhou F. (2017) Trafficking and other regulatory mechanisms for organic anion transporting polypeptides and organic anion transporters that modulate cellular drug and xenobiotic influx and that are dysregulated in disease. Br J Pharmacol, 174 (13): 1908-1924. [PMID:28299773]

Niemi M, Pasanen MK, Neuvonen PJ. (2011) Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev, 63 (1): 157-81. [PMID:21245207]

Obaidat A, Roth M, Hagenbuch B. (2012) The expression and function of organic anion transporting polypeptides in normal tissues and in cancer. Annu Rev Pharmacol Toxicol, 52: 135-51. [PMID:21854228]

* Roth M, Obaidat A, Hagenbuch B. (2012) OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br J Pharmacol, 165 (5): 1260-87. [PMID:22013971]

Shitara Y, Maeda K, Ikejiri K, Yoshida K, Horie T, Sugiyama Y. (2013) Clinical significance of organic anion transporting polypeptides (OATPs) in drug disposition: their roles in hepatic clearance and intestinal absorption. Biopharm Drug Dispos, 34 (1): 45-78. [PMID:23115084]

Shitara Y, Sugiyama Y. (2017) Preincubation-dependent and long-lasting inhibition of organic anion transporting polypeptide (OATP) and its impact on drug-drug interactions. Pharmacol Ther, 177: 67-80. [PMID:28249706]

Stieger B, Hagenbuch B. (2014) Organic anion-transporting polypeptides. Curr Top Membr, 73: 205-32. [PMID:24745984]

* Zamek-Gliszczynski MJ, Taub ME, Chothe PP, Chu X, Giacomini KM, Kim RB, Ray AS, Stocker SL, Unadkat JD, Wittwer MB et al.. (2018) Transporters in Drug Development: 2018 ITC Recommendations for Transporters of Emerging Clinical Importance. Clin Pharmacol Ther, 104 (5): 890-899. [PMID:30091177]

1. Bailey DG, Dresser GK, Leake BF, Kim RB. (2007) Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice. Clin Pharmacol Ther, 81 (4): 495-502. [PMID:17301733]

2. Bednarczyk D, Boiselle C. (2016) Organic anion transporting polypeptide (OATP)-mediated transport of coproporphyrins I and III. Xenobiotica, 46 (5): 457-66. [PMID:26383540]

3. Chan BS, Satriano JA, Pucci M, Schuster VL. (1998) Mechanism of prostaglandin E2 transport across the plasma membrane of HeLa cells and Xenopus oocytes expressing the prostaglandin transporter "PGT". J Biol Chem, 273 (12): 6689-97. [PMID:9506966]

4. Fehrenbach T, Cui Y, Faulstich H, Keppler D. (2003) Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins. Naunyn Schmiedebergs Arch Pharmacol, 368 (5): 415-20. [PMID:14530907]

5. Fischer WJ, Altheimer S, Cattori V, Meier PJ, Dietrich DR, Hagenbuch B. (2005) Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin. Toxicol Appl Pharmacol, 203 (3): 257-63. [PMID:15737679]

6. Gui C, Obaidat A, Chaguturu R, Hagenbuch B. (2010) Development of a cell-based high-throughput assay to screen for inhibitors of organic anion transporting polypeptides 1B1 and 1B3. Curr Chem Genomics, 4: 1-8. [PMID:20448812]

7. Kanai N, Lu R, Satriano JA, Bao Y, Wolkoff AW, Schuster VL. (1995) Identification and characterization of a prostaglandin transporter. Science, 268 (5212): 866-9. [PMID:7754369]

8. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P. (2012) Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem, 55 (10): 4740-63. [PMID:22541068]

9. Noé J, Portmann R, Brun ME, Funk C. (2007) Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab Dispos, 35 (8): 1308-14. [PMID:17470528]

10. Treiber A, Schneiter R, Häusler S, Stieger B. (2007) Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos, 35 (8): 1400-7. [PMID:17496208]

11. Vavricka SR, Van Montfoort J, Ha HR, Meier PJ, Fattinger K. (2002) Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology, 36 (1): 164-72. [PMID:12085361]

Bruno Hagenbuch Dept. Pharmacology, Toxicology and Therapeutics KU Medical Center 3901 Rainbow Blvd. Kansas City Kansas 66160 USA