Functional analysis of four naturally occurring variants of human constitutive androstane receptor was written by Ikeda, Shinobu;Kurose, Kouichi;Jinno, Hideto;Sai, Kimie;Ozawa, Shogo;Hasegawa, Ryuichi;Komamura, Kazuo;Kotake, Takeshi;Morishita, Hideki;Kamakura, Shiro;Kitakaze, Masafumi;Tomoike, Hitonobu;Tamura, Tomohide;Yamamoto, Noboru;Kunitoh, Hideo;Yamada, Yasuhide;Ohe, Yuichiro;Shimada, Yasuhiro;Shirao, Kuniaki;Kubota, Kaoru;Minami, Hironobu;Ohtsu, Atsushi;Yoshida, Teruhiko;Saijo, Nagahiro;Saito, Yoshiro;Sawada, Jun-ichi. And the article was included in Molecular Genetics and Metabolism in 2005.Computed Properties of C19H12Cl3N3OS This article mentions the following:
The human constitutive androstane receptor (CAR, NR1I3) is a member of the orphan nuclear receptor superfamily that plays an important role in the control of drug metabolism and disposition. In this study, we sequenced all the coding exons of the NR1I3 gene for 334 Japanese subjects. We identified three novel single nucleotide polymorphisms (SNPs) that induce non-synonymous alterations of amino acids (His246Arg, Leu308Pro, and Asn323Ser) residing in the ligand-binding domain of CAR, in addition to the Val133Gly variant, which was another CAR variant identified in our previous study. We performed functional anal. of these four naturally occurring CAR variants in COS-7 cells using a CYP3A4 promoter/enhancer reporter gene that includes the CAR responsive elements. The His246Arg variant caused marked reductions in both transactivation of the reporter gene and in the response to 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO), which is a human CAR-specific agonist. The transactivation ability of the Leu308Pro variant was also significantly decreased, but its responsiveness to CITCO was not abrogated. The transactivation ability and CITCO response of the Val133Gly and Asn323Ser variants did not change as compared to the wild-type CAR. These data suggest that the His246Arg and Leu308Pro variants, especially His246Arg, may influence the expression of drug-metabolizing enzymes and transporters that are transactivated by CAR. 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: 338404-52-7Computed Properties of C19H12Cl3N3OS).
6-(4-Chlorophenyl)imidazo[2,1-b]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl) oxime (cas: 338404-52-7) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. Thiazole sulfonation occurs only under forcing conditions: the action of oleum at 250 掳C for 3 hours in the presence of mercury(II) sulfate leads to 65% formation of 5-thiazole sulfonic acid.Computed Properties of C19H12Cl3N3OS
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica