Ensemble Docking Approach to Mitigate Pregnane X Receptor-Mediated CYP3A4 Induction Risk

• Published in: Journal of chemical information and modeling Vol. 63; no. 1; pp. 173 - 186
• Main Authors: Chen, Qi, Zhou, Xin, Rehmel, Jessica, Steele, James P., Svensson, Kjell A., Beck, James P., Hembre, Erik J., Hao, Junliang
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 09.01.2023
• Subjects: Binding; Computational Chemistry; Cytochrome P-450 CYP3A - metabolism; Docking; Dopamine; Enzyme Induction; Homology; Modulators; Pregnane X Receptor - metabolism; Receptors; Receptors, Steroid - chemistry; Receptors, Steroid - genetics; Receptors, Steroid - metabolism; Scaffolds

Three structurally closely related dopamine D1 receptor positive allosteric modulators (D1 PAMs) based on a tetrahydroisoquinoline (THIQ) scaffold were profiled for their CYP3A4 induction potentials. It was found that the length of the linker at the C5 position greatly affected the potentials of the...