Fig. 6: Trade-off between potency and selectivity of SCM-18 analogs.

a–c Chemical structures of (a) SCM-24, (b) SCM-25 and (c) SCM-26 and dose–response curves showing their concentration-dependent inhibition of CYP3A4/5. Percentage inhibition data were normalized against DMSO controls (as 0% inhibition) and 30 µM ketoconazole controls (as 100% inhibition). The reported numerical values are the means and standard deviations of the IC₅₀ values calculated from triplicate experiments (n = 3). d–f Overlay of CYP3A4–SCM-18 (pink) with (d) CYP3A4–SCM-24 (yellow), (e) CYP3A4–SCM-25 (yellow), (f) CYP3A4–SCM-26 (yellow) crystal structures highlighting unique interactions associated with these analogs. For stick representations in (d–f), fluoride atoms are colored in cyan, chloride atoms are colored in green, nitrogen atoms are colored in blue, and oxygen atoms are colored in red. Source data for (a–c) are provided as a Source Data file.