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*Correspondence: Kai Liang, [email protected] This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology Disclaimer All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers

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Further investigations are needed to address these knowledge gaps

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Although the maximum plasma concentration is lower when compound 2 is administered PO (0.77 M) instead of IP (4.8 M), it is still 4.3-fold higher than LD 50 for ex vivo NTS determined in the commonly used 72 h assay, also indicating that TGR inhibitor 2 is orally bioavailable and the initial prediction of oral bioavailability based on the Lipinski et al