**5. Conclusions**

Mertansine inhibited UGT1A1, UGT1A3, and UGT1A4 enzyme activities in human liver microsomes and dose-dependently suppressed the mRNA levels of CYP1A2, CYP2B6, CYP3A4, CYP2C8, CYP2C9, CYP2C19, UGT1A1, UGT1A4, and UGT1A9 after 48 h treatment of 1.25–2500 nM mertansine in three human hepatocytes. Additionally, mertansine treatment resulted in the decrease of CYP1A2, CYP2B6, and CYP3A4 enzyme activities. These in vitro DDI potentials of mertansine with substrate drugs for major CYPs and UGTs enzymes indicate that the evaluation of the DDI potentials of ADC candidates with mertansine as a payload is necessary.

**Author Contributions:** Conceptualization, W.-G.C. and H.S.L.; methodology, W.-G.C., R.P., D.K.K., Y.S., and Y.-Y.C.; software, W.-G.C., R.P. and H.S.L.; investigation, W.-G.C., R.P., D.K.K., and Y.S.; data curation, W.-G.C. and H.S.L.; writing—original draft preparation, W.-G.C. and D.K.K.; writing—review and editing, Y.-Y.C. and H.S.L.; supervision, H.S.L.; project administration, H.S.L.; funding acquisition, H.S.L. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI12C1852) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2015M3A9E1028325).

**Conflicts of Interest:** The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
