Solute carrier organic anion transporter family member 1B1, 1B3, 2B1 and ATP-binding cassette sub-family G member 2 (OATP1B1, OATP1B3, OATP2B1, and BCRP)

The group comprising OATP1B1, OATP1B3, OATP2B1, and BCRP represents a critical set of membrane transporters that govern the pharmacokinetics and safety of numerous drugs (FDA, 2020). OATP1B1 (SLCO1B1), OATP1B3 (SLCO1B3), and OATP2B1 (SLCO2B1) are solute carrier transporters primarily responsible for the hepatic uptake of endogenous compounds like bilirubin and exogenous drugs such as statins (UniProt P46721, Q9NPD5, O95281). BCRP (ABCG2) is an ATP-binding cassette efflux transporter found in the intestine, liver, and blood-brain barrier, where it limits drug absorption and facilitates excretion (UniProt Q9UNQ0). These transporters are major determinants of clinically significant drug-drug interactions (DDIs); for instance, inhibition of OATP1B1/1B3 can lead to markedly increased plasma concentrations of statins, raising the risk of life-threatening myopathy (Niemi et al., 2011). Genetic variants in these transporters, particularly the SLCO1B1*5 allele, are associated with altered drug efficacy and increased toxicity profiles (CPIC, 2022). Endogenous biomarkers like Coproporphyrin I and III are increasingly utilized in clinical development to assess the in vivo inhibition of these transporters without the need for complex probe drug cocktails (Chu et al., 2018). Because of their collective impact on drug disposition, regulatory agencies require the evaluation of new molecular entities as potential substrates or inhibitors of these specific transporters.

Other names

SLCO1B1SLCO1B3SLCO2B1ABCG2OATP-COATP-8OATP-BBreast cancer resistance proteinMitoxantrone resistance-associated proteinPlacenta-specific ABC transporter

Drugs interact with these transporters as substrates, where they are physically moved across cellular membranes, or as inhibitors and inducers that modulate the transport activity for other co-administered compounds (FDA, 2020). OATPs facilitate sodium-independent uptake of organic anions into hepatocytes, while BCRP utilizes ATP hydrolysis to pump substrates out of cells into the bile, urine, or intestinal lumen (UniProt P46721, Q9UNQ0).