Assessing Trans-Inhibition of OATP1B1 and OATP1B3 by Calcineurin and/or PPIase Inhibitors and Global Identification of OATP1B1/3-Associated Proteins.

ABSTRACT: Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are key determinants of drug-drug interactions (DDIs). Various drugs including the calcineurin inhibitor (CNI) cyclosporine A (CsA) exert preincubation-induced trans-inhibitory effects upon OATP1B1 and/or OATP1B3 (abbreviated as OATP1B1/3) by unknown mechanism(s). OATP1B1/3 are phosphoproteins; calcineurin, which dephosphorylates and regulates numerous phosphoproteins, has not previously been investigated in the context of preincubation-induced trans-inhibition of OATP1B1/3. Herein, we compare the trans-inhibitory effects exerted on OATP1B1 and OATP1B3 by CsA, the non-analogous CNI tacrolimus, and the non-CNI CsA analogue SCY-635 in transporter-overexpressing human embryonic kidney (HEK) 293 stable cell line

SUBMITTER: Powell JT 

PROVIDER: S-EPMC10818623 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature