OATPs

Organic Anion Transporting Polypeptides (OATPs/SLCO) are a family of membrane transporters that mediate the uptake of a wide range of endogenous compounds and drugs. While some OATPs are broadly expressed throughout the body, others show highly tissue-specific expression patterns, with notable differences between species.

Several OATP family members are expressed in the brain, including OATP1A2 (SLCO1A2), OATP1C1 (SLCO1C1), OATP2A1 (SLCO2A1), OATP2B1 (SLCO2B1), and OATP3A1 (SLCO3A1). Importantly, these transporters exhibit distinct cellular and anatomical expression patterns. For example, OATP1A2 and OATP2B1 are expressed at the blood–brain barrier, OATP3A1 is primarily found in neurons, and OATP1C1 is highly expressed in astrocytes. These selective expression profiles provide unique opportunities for transporter-mediated brain and intra-brain drug delivery.

OATPs are sodium-independent transporters that recognize structurally diverse substrates, including hormones, metabolites, and therapeutic compounds. Their broad substrate specificity and tissue-selective expression make them attractive targets for drug delivery applications.

Our research focuses particularly on OATP1A2 and OATP1C1 as potential carriers for brain-, cell-, and tissue-selective drug delivery. We investigate their expression, transport mechanisms, and suitability for the development of novel transporter-utilizing drugs and prodrugs.

Selected Publications

Tonduru, A. K.; Maljaei, S. H.; Adla, S. K.; Anamea, L.; Espada1, C.; Santos, I. F.; Montaser, A. B.; Rautio, J.; Kronenberger, T.; Poso, A.; Huttunen, K. M. Targeting Glial Cells by Organic Anion Transporting Polypeptide 1C1 (OATP1C1) -Utilizing L-Thyroxine-Derived Prodrugs. Journal of Medicinal Chemistry, 2023,66(22):15094-15114. https://doi.org/10.1021/acs.jmedchem.3c01026

Tonduru, A. K.; Adla, S. K.; Huttunen, K. M.; Kronenberger, T.; Poso, A. Comparative Modelling of Organic Anion Transporting Polypeptides: Structural Insights and Comparison of Binding Modes. Molecules, 2021, 7(23), 8531. https://doi.org/10.3390/molecules27238531

Adla, S. K.; Tonduru, A. K.; Kronenberger, T.; Kudova, E.; Poso, A.; Huttunen, K. M. Neurosteroids: Structure-Uptake Relationships and Computational Modeling of Organic Anion Transporting Polypeptides (OATP)1A2. Molecules, 2021, 26(18): 5662. https://doi.org/10.3390/molecules26185662