Quantitative Analysis of the Interaction of Constitutive Androstane Receptor with Chemicals and Steroid Receptor Coactivator 1 Using Surface Plasmon Resonance Biosensor Systems: A Case Study of the Baikal Seal (Pusa sibirica) and the Mouse was written by Dau, Pham Thi;Sakai, Hiroki;Hirano, Masashi;Ishibashi, Hiroshi;Tanaka, Yuki;Kameda, Kenji;Fujino, Takahiro;Kim, Eun-Young;Iwata, Hisato. And the article was included in Toxicological Sciences in 2013.Quality Control of 6-(4-Chlorophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl) oxime This article mentions the following:
The constitutive androstane receptor (CAR) not only displays a high basal transcriptional activity but also acts as a ligand-dependent transcriptional factor. It is known that CAR exhibits different ligand profiles across species. However, the mechanisms underlying CAR activation by chems. and the species-specific responses are not fully understood. The objectives of this study are to establish a high-throughput tool to screen CAR ligands and to clarify how CAR proteins from the Baikal seal (bsCAR) and the mouse (mCAR) interact with chems. and steroid receptor coactivator 1 (SRC1). The authors developed the surface plasmon resonance (SPR) system to assess quant. the interaction of CAR with potential ligands and SRC1. The ligand-binding domain (LBD) of bsCAR and mCAR was synthesized in a wheat germ cell-free system. The purified CAR LBD was then immobilized on the sensor chip for the SPR assay, and the kinetics of direct interaction of CARs with ligand candidates was measured. Androstanol and androstenol, estrone, 17β-estradiol, TCPOBOP, and CITCO showed compound-specific but similar affinities for both CARs. The CAR-SRC1 interaction was ligand dependent but exhibited a different ligand profile between the seal and the mouse. The results of SRC1 interaction assay accounted for those of the authors’ previous in vitro CAR-mediated transactivation assay. In silico analyses also supported the results of CAR-SRC1 interaction; there is little structural difference in the ligand-binding pocket of bsCAR and mCAR, but there is a distinct discrimination in the helix 11 and 12 of these receptors, suggesting that the interaction of ligand-bound CAR and SRC1 is critical for determining species-specific and ligand-dependent transactivation over the basal activity. The SPR assays demonstrated a potential as a high-throughput screening tool of CAR ligands. In the experiment, the researchers used many compounds, for example, 6-(4-Chlorophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl) oxime (cas: 338404-52-7Quality Control of 6-(4-Chlorophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl) oxime).
6-(4-Chlorophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl) oxime (cas: 338404-52-7) belongs to thiazole derivatives. The thiazole ring is notable as a component of the vitamin thiamine (B1). The nitrogen in thiazole is sp2 hybridized and the lone pair of electrons localized on the nitrogen is less reactive due to increased aromatic character and decreased basicity. It is protonated and alkylated/acylated at nitrogen forming hydrochloride and quaternary thiazolium salt.Quality Control of 6-(4-Chlorophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl) oxime
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica