SLC Transporter Inhibition

Human SLC transporter inhibition is in our portfolio of in vitro drug transporter services. Cyprotex delivers consistent, high quality data in line with our published transporter strategy review, for either your early stage screening projects or your later stage regulatory studies according to FDA, EMA, PMDA and ICH guidance.

The impact of SLC transporter inhibition and its measurement in vitro:

• The SLC (solute carrier) super family of transporter proteins, transport a wide range of different solutes across biological membranes using diverse energy coupling mechanisms¹.
• SLC transporters include the OATP, OAT, OCT, MATE, OCTN, and the PEPT families. These transporters are expressed in the intestine, the blood brain barrier, the kidneys and the liver where they influence the absorption, distribution, metabolism and excretion of drugs within the body.
• The regulatory guidance^2-3 recommends investigating your test article for potential OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1 and MATE2-K inhibition due to the role of these transporters in clinical drug-drug interactions The EMA³ and the International Transporter Consortium (ITC)⁴ also suggests that potential interactions with OCT1 should be considered, particularly if co-administering with the narrow therapeutic index medication fenoterol.
• The EMA³ and the International Transporter Consortium (ITC)⁴ also suggests that potential interactions with OCT1 should be considered, particularly if co-administering with the narrow therapeutic index medication fenoterol.
• Cyprotex’s SLC transporter inhibition assay determines if your test article is an inhibitor of the key transporters recommended in the regulatory guidance. Additionally, since 2016 and ahead of guidance recommendations for IC₅₀ determination, the assay has incorporated a preincubation step with test compound for OATP1B1, OATP1B3 as well as for all other transporters¹.

_{1) Elsby R et al., (2022) Studying the right transporter at the right time: an in vitro strategy for assessing drug-drug interaction risk during drug discovery and development. Expert Opin Drug Metab Toxicol 18(10): 619-655
2) FDA Guidance for Industry – In Vitro Drug Interaction Studies - Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions (January 2020)
3) The European Medicines Agency (EMA) Guideline on the Investigation of Drug Interactions (Adopted 2012)
4) Zamek-Gliszczynski M et al., (2018) Transporters in Drug Development: 2018 ITC Recommendations for Transporters of Emerging Clinical Importance. Clin Pharmacol Ther 104(5): 890-899}