P1, N=24, Completed, Kaken Pharmaceutical | Not yet recruiting --> Completed

Among the tested PPIs (lansoprazole, omeprazole, rabeprazole, and esomeprazole), the inhibitory effect of esomeprazole on hOCT2-mediated L-OHP transport was greater than those of other PPIs. Thus, to the best of our knowledge, our study demonstrates for the first time that concomitant esomeprazole prevents OIPN, at least in part, by inhibiting OCT2-mediated L-OHP transport into the DRG, thus decreasing L-OHP accumulation in the DRG. These findings provide important information for the establishment of novel protective approaches to minimize OIPN.

P1, N=40, Completed, Kaken Pharmaceutical | Active, not recruiting --> Completed

P1, N=16, Completed, Kokua Pharma Inc. | Recruiting --> Completed

P1, N=38, Completed, Kaken Pharmaceutical | Active, not recruiting --> Completed

P1, N=40, Active, not recruiting, Kaken Pharmaceutical | Recruiting --> Active, not recruiting

P1, N=36, Not yet recruiting, Kaken Pharmaceutical

Moreover, dequalinium inhibited hOCT2-mediated transport of platinum anti-cancer agents (cisplatin and oxaliplatin) in a concentration-dependent manner. Our study is the first to demonstrate the construction of a novel machine learning-based QSAR model for hOCT2 inhibitors and identify a novel hOCT2 inhibitor among FDA-approved drugs using this model.

P1, N=40, Recruiting, Kaken Pharmaceutical

Although 3 µM dasatinib reduced 100 µM OHP accumulation in hOCT2-HEK293 cells, co-incubation with dasatinib and OHP did not prevent OHP toxicity, possibly due to dasatinib-induced cell viability reduction. In summary, this study demonstrates OHP as an OCT2 substrate and dasatinib as a non-transported inhibitor and regulator of OCT2, offering potential for OIPN mitigation.

This study investigated the interaction between the already approved cationic drugs disopyramide, imipramine, and orphenadrine with hOCT2 that is stably expressed in human embryonic kidney cells. In conclusion, certain interventions targeting hOCT2 have demonstrated the ability to reduce CDDP cytotoxicity, at least in vitro. Further investigations in in vivo systems are warranted to ascertain their potential applicability as co-treatments for mitigating undesired toxicities associated with CDDP in patients.

CircSLC22A23 regulated the transcription of EGFR through activation of HNRNPU in GC cells, suggesting that circSLC22A23 may serve as a potential therapeutic target for the treatment of GC.