Additional file 1 of Radiolabeled 15-mer peptide internalization is mediated by megalin (LRP2 receptor) in a CRISPR/Cas9-based LRP2 knockout human kidney cell model

Additional file 1. The additional file contains information pertaining to the detailed methodology of sgRNA design, peptide synthesis, radiolabeling and purity control, additional results of flow cytometry analysis and FACS sorting, full-length Western blot images, and radiochromatograms of both peptides

2‑(3-Methoxyphenyl)quinazoline Derivatives: A New Class of Direct Constitutive Androstane Receptor (CAR) Agonists

Constitutive androstane receptor (CAR) is a key regulator of xenobiotic and endobiotic metabolism. Together with pregnane X (PXR) and aryl hydrocarbon (AHR) receptors, it is referred to as “xenobiotic receptor”. The unique properties of human CAR, such as its high constitutive activity, both direct (ligand-binding domain-dependent) and indirect activation have hindered the discovery of direct selective human CAR ligands. Herein, we report a novel class of direct human CAR agonists in a group of 2-(3-methoxyphenyl)­quinazoline derivatives. The compounds are even more potent activators of human CAR than is prototype 6-(4-chlorophenyl)­imidazo­[2,1-<i>b</i>]­[1,3]­thiazole-5-carbaldehyde <i>O</i>-(3,4-dichlorobenzyl)­oxime (CITCO). The three most potent ligands are at the same time extremely potent activators of the other xenobiotic or hormonal receptors, namely PXR, AHR, and vitamin D receptor, which regulate major xenobiotic-metabolizing enzymes and efflux transporters. Thus, the novel CAR ligands can be also considered as constituting the first class of potent pan-xenobiotic receptor ligands that can serve as potential antidotes boosting overall metabolic elimination of xenobiotic or toxic compounds

2‑(3-Methoxyphenyl)quinazoline Derivatives: A New Class of Direct Constitutive Androstane Receptor (CAR) Agonists

Constitutive androstane receptor (CAR) is a key regulator of xenobiotic and endobiotic metabolism. Together with pregnane X (PXR) and aryl hydrocarbon (AHR) receptors, it is referred to as “xenobiotic receptor”. The unique properties of human CAR, such as its high constitutive activity, both direct (ligand-binding domain-dependent) and indirect activation have hindered the discovery of direct selective human CAR ligands. Herein, we report a novel class of direct human CAR agonists in a group of 2-(3-methoxyphenyl)­quinazoline derivatives. The compounds are even more potent activators of human CAR than is prototype 6-(4-chlorophenyl)­imidazo­[2,1-<i>b</i>]­[1,3]­thiazole-5-carbaldehyde <i>O</i>-(3,4-dichlorobenzyl)­oxime (CITCO). The three most potent ligands are at the same time extremely potent activators of the other xenobiotic or hormonal receptors, namely PXR, AHR, and vitamin D receptor, which regulate major xenobiotic-metabolizing enzymes and efflux transporters. Thus, the novel CAR ligands can be also considered as constituting the first class of potent pan-xenobiotic receptor ligands that can serve as potential antidotes boosting overall metabolic elimination of xenobiotic or toxic compounds