OATP2B1 (SLCO2B1, formerly OATP-B) is a member of the Organic Anion Transporting Polypeptide family of drug transporters. It is a membrane protein that facilitates cellular entry of its substrates and is ubiquitously expressed in the human organism. Its high abundance in intestine, liver and kidney is assumed to influence the handling of its substrates in these organs of pharmacokinetic relevance [1].

In the past, we have conducted multiple studies on the expression and function of OATP2B1 [2, 3, 4, 5]. Within those studies we have identified and characterized substrates [4, 5, 6, 8]. Moreover, we were able to describe mechanisms modifying its transcription [6] and mechanisms modifying its activity (post-transcriptional interaction with PDZK1) [7], whereby linking OATP2B1 more and more to other functions, but drug transport.

After identifying pronounced species-differences in substrate recognition [9], we were following up on the role of OATP2B1 in in vivo pharmacokinetics and brain disposition, respectively. In our studies we applied atorvastatin [11], erlotinib [12] and the steroid metabolite pregnenolone-sulfate [13] to determine how these substrates of OATP2B1 behave in vivo. This allowed us to examine the impact of OATP2B1 on systemic drug exposure and to explore its involvement in tissue distribution, including, but not limited to, the brain.

[1] OATP2B1 - The underrated member of the organic anion transporting polypeptide family of drug transporters? Kinzi J, Grube M, Meyer zu Schwabedissen HE. Biochem Pharmacol. 2021;188:114534. (https://doi.org/10.1016/j.bcp.2021.114534 )

[2] Organic anion transporting polypeptide 2B1 and breast cancer resistance protein interact in the transepithelial transport of steroid sulfates in human placenta. Grube M, Reuther S, Meyer zu Schwabedissen H, Köck K, Draber K, Ritter CA, Fusch C, Jedlitschky G, Kroemer HK. Drug Metab Dispos. 2007;35(1):30-5. (https://doi.org/10.1124/dmd.106.011411 )

[3] Characterization of OATP1B3 and OATP2B1 transporter expression in the islet of the adult human pancreas. Kim M, Deacon P, Tirona RG, Kim RB, Pin CL, Meyer zu Schwabedissen HE, Wang R, Schwarz UI. Histochem Cell Biol. 2017;148(4):345-357. (https://doi.org/10.1007/s00418-017-1580-6)

[4] OATP1A2 and OATP2B1 Are Interacting with Dopamine-Receptor Agonists and Antagonists. Schäfer AM, Meyer zu Schwabedissen HE, Bien-Möller S, Hubeny A, Vogelgesang S, Oswald S, Grube M. Mol Pharm.2020;17(6):1987-1995. (https://doi.org/10.1021/acs.molpharmaceut.0c00159)

[5] Expression of OATP2B1 as determinant of drug effects in the microcompartment of the coronary artery. Hussner J, Begunk R, Boettcher K, Gliesche DG, Prestin K, Meyer zu Schwabedissen HE. Vascul Pharmacol. 2015;72:25-34. (https://doi.org/10.1016/j.vph.2015.06.006 )

[6] Thyroid Hormones Are Transport Substrates and Transcriptional Regulators of Organic Anion Transporting Polypeptide 2B1. Meyer zu Schwabedissen HE, Ferreira C, Schaefer AM, Oufir M, Seibert I, Hamburger M, Tirona RG. Mol Pharmacol. 2018;94(1):700-712. (https://doi.org/10.1124/mol.117.111161 )

[7] The scaffold protein PDZK1 modulates expression and function of the organic anion transporting polypeptide 2B1. Ferreira C, Hagen P, Stern M, Hussner J, Zimmermann U, Grube M, Meyer zu Schwabedissen HE. Eur J Pharm Sci. 2018;120:181-190. (https://doi.org/10.1016/j.ejps.2018.05.006 )

[8] Hyperforin-Induced Activation of the Pregnane X Receptor Is Influenced by the Organic Anion-Transporting Polypeptide 2B1. Schäfer AM, Potterat O, Seibert I, Fertig O, Meyer zu Schwabedissen HE. Mol Pharmacol. 2019;95(3):313-323. doi: 10.1124/mol.118.114066.  (https://www.ncbi.nlm.nih.gov/pubmed/30573512 )

[9] Differences in transport function of the human and rat orthologue of the Organic Anion Transporting Polypeptide 2B1 (OATP2B1). Hussner J, Foletti A, Seibert I, Fuchs A, Schuler E, Malagnino V, Grube M, Meyer zu Schwabedissen HE. Drug Metab Pharmacokinet. 2021;41:100418. (https://doi.org/10.1016/j.dmpk.2021.100418)

[10] The influence of OATP2B1 and atorvastatin on coproporphyrin isomers in rats. Kinzi J, Grube M, Hussner J, Seibert I, Hamburger M, Meyer zu Schwabedissen HE. J Pharmacol Sci. 2023;153(3):170-174. (https://doi.org/10.1016/j.jphs.2023.09.003 )

[11] Impact of OATP2B1 on Pharmacokinetics of Atorvastatin Investigated in rSlco2b1-Knockout and SLCO2B1-Knockin Rats. Kinzi J, Hussner J, Seibert I, Vythilingam M, Vonwyl C, Gherardi C, Detampel P, Schwardt O, Ricklin D, Meyer zu Schwabedissen HE. Drug Metab Dispos. 2024;52(9):957-965. (https://doi.org/10.1124/dmd.124.001686 )

[12] Humanization of SLCO2B1 in Rats Increases rCYP3A1 Protein Expression but Not the Metabolism of Erlotinib to OSI-420. Rysz M, Schäfer AM, Paloumpis N, Kinzi J, Brecht K, Seibert I, Schmidlin S, In-Albon K, Ricklin D, Meyer zu Schwabedissen HE. J Pharmacol Exp Ther. 2024;389(1):87-95. (https://doi.org/10.1124/jpet.123.001884 ).

[13] Pregnenolone Sulfate Permeation at the Blood-Brain Barrier is Independent of OATP2B1-In Vivo and In Vitro Insights. Taggi V, Schäfer AM, Oswald S, Kinzi JH, Seibert I, Al-Khatib A, Meyer zu Schwabedissen HE. Biopharm Drug Dispos. 2025;46(1):33-46. (https://doi.org/10.1002/bdd.70002 )