Structural and functional biochemistry of OATP1B3: from polymorphisms to therapeutic targets

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Abstract

INTRODUCTION: Organic Anion Transporting Polypeptide 1B3 (OATP1B3) plays a key role in hepatic transport of endogenous compounds, xenobiotics and drugs. In recent years, new data have been presented on the molecular organization, mechanisms of function and regulation, genetic polymorphisms of OATP1B3, and its clinical significance in pharmacokinetics, diagnosis and treatment. Of particular interest is the extrahepatic expression of the transporter, which opens new prospects for targeted therapy.

AIM: To identify the structural and functional biochemical features of OATP1B3 transporter, its genetic polymorphisms and their impact on pharmacokinetic and therapeutic properties, determine the potential of OATP1B3 for targeted and personalized medicine.

Literature search was conducted using the following keywords: OATP1B3, SLCO1B3, transporter, substrate specificity, regulation, oncology, and hepatocellular carcinoma in Russian and English. Electronic databases providing access to peer-reviewed scientific articles were used: eLibrary, Medline/PubMed, and Google Scholar. The search was conducted between 2000 and 2004 to cover the current data, starting from the first publications on OATP1B3 identification, but also taking into account earlier key works on OATP1B3 identification.

This review presents the biochemical features of OATP1B3 localization, structure, and transport cycle. It also systematizes literature data on substrates, inhibitors, and inducers of the transporter protein, describes regulatory mechanisms and identifies the clinical significance of this transporter protein. OATP1B3 is demonstrated to have tissue-specific localization: it is normally expressed in the liver, but in oncologic pathologies is detected in the cytosol of gastrointestinal and lung tumor cells, where it may participate in signaling pathways. Evidence of high genetic variability of the SLCO1B3 gene is presented. The clinical potential of OATP1B3 is confirmed by its role in diagnostics (liver MRI with gadoxetate) and the possibility of targeted delivery of chemotherapeutic drugs.

CONCLUSION: OATP1B3 is an influx transporter protein that has an important clinical significance participating in transport of statins, cytostatics and diagnostic contrast agents, and its activity is modulated by post-translational modifications.

About the authors

Yuliya V. Abalenikhina

Ryazan State Medical University

Author for correspondence.
Email: abalenihina88@mail.ru
ORCID iD: 0000-0003-0427-0967
SPIN-code: 4496-9027

MD, Dr. Sci. (Medicine), Assistant Professor

Russian Federation, Ryazan

Pelageya D. Ananyeva

Ryazan State Medical University

Email: erokhina.pelageya96@yandex.ru
ORCID iD: 0000-0003-4802-5656
SPIN-code: 1480-6854

MD, Cand. Sci. (Medicine)

Russian Federation, Ryazan

Aleksey V. Shchulkin

Ryazan State Medical University

Email: alekseyshulkin@rambler.ru
ORCID iD: 0000-0003-1688-0017
SPIN-code: 2754-1702

MD, Dr. Sci. (Medicine), Assistant Professor

Russian Federation, Ryazan

Ekaterina D. Mikryukova

Ryazan State Medical University

Email: kate.mikrukova@yandex.ru
ORCID iD: 0009-0006-6457-4777
Russian Federation, Ryazan

Pavel Y. Mylnikov

Ryazan State Medical University

Email: dukeviperlr@gmail.com
ORCID iD: 0000-0001-7829-2494
SPIN-code: 8503-3082

Cand. Sci. (Biology)

Russian Federation, Ryazan

Anna E. Mezina

Ryazan State Medical University

Email: mezinaanya@yandex.ru
ORCID iD: 0009-0000-0238-4771
Russian Federation, Ryazan

Elena N. Yakusheva

Ryazan State Medical University

Email: e.yakusheva@rzgmu.ru
ORCID iD: 0000-0001-6887-4888
SPIN-code: 2865-3080

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Ryazan

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