**4. Conclusions**

In conclusion, we report that selamariscina A is a strong CYP2C8 and CYP2C9 inhibitor. When evaluated for amodiaquine *O*-deethylation and diclofenac hydroxylation inhibitory activity against CYP2C8 and CYP2C9, as well as seven other P450s, it exhibited above 50-fold selectivity. Like montelukast and sulfaphenazole, selamariscina A could be useful as a strong CYP2C8 and CYP2C9 inhibitor in P450 phenotyping studies when HLMs are the enzyme source. Additionally, selamariscina A might cause clinically relevant pharmacokinetic drug interactions with other co-administered drugs

metabolized by CYP2C8 or CYP2C9. These in vitro findings provide primary data for future in vivo animal and clinical studies on risk prediction related to the interaction of drugs with herbs.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/1999-4923/12/4/343/s1, Figure S1: Representative Lineweaver–Burk plots obtained from a kinetic study of CYP1A2-catalyzed phenacetin *O*-deethylation (A), CYP2B6-catalyzed bupropion hydroxylation (B), CYP2C8-catalyzed amodiaquine *N*-deethylation (C), CYP2C8-catalyzed rosiglitazone 5-hydroxylation (D), CYP2C9-catalyzed diclofenac 4-hydroxylation (E), and CYP3A-catalyzed midazolam 1-hydroxylation (F) in the presence of di fferent concentrations of selamariscina A. Each data point shown represent the mean ± standard error in triplicate samples.

**Author Contributions:** S.-Y.P. and K.-H.L. conceived and designed the experiments; S.-Y.P., P.-H.N., G.K., S.-N.J., G.-H.L., and N.M.P. performed experiments; S.-Y.P., Z.W., and K.-H.L. analyzed the data; S.-Y.P. and K.-H.L. wrote the paper. All authors have read and agreed to the published version of the manuscript.

**Funding:** This study was supported by the National Research Foundations of Korea, Ministry of Science and ICT, Republic of Korea [NRF-2019R1A2C1008713], a Korea Basic Science Institute National Research Facilities & Equipment Center gran<sup>t</sup> funded by the Korea governmen<sup>t</sup> (Ministry of Education) [2019R1A6C1010001], and the National Foundation for Science and Technology Development of Vietnam, Ministry of Science and Technology [NAFOSTED-104.01-2017.50].

**Conflicts of Interest:** The authors declare no conflict of interest. N.M.P. is from Vietnam Hightech of Medicinal and Pharmaceutical JSC, the company lease state 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.
