絞り込み

16548

広告

中国 仏技術採用の新型原発 世界初の営業運転

原子力発電所の建設を積極的に推し進めている中国で、フランスの技術を採用した新型の原発が世界で初めて営業運転を開始し、東京電力福島第一原子力発電所の事故を受けて、...

  1. スマブラ「灯火の星」セリフ・低予算版&カ...
  2. 企業活動の及ぼす環境影響を貨幣価値に換算...
  3. [企業] Axovant社 ガングリオシ...
  4. 月10冊を目標に読書をはじめてから気づい...

ニュース一覧

Identification of a Novel Metabolite of Vildagliptin in Humans: Cysteine Targets the Nitrile Moiety to Form a Thiazoline Ring.

著者 Mizuno K , Takeuchi K , Umehara K , Nakajima M
Biochem Pharmacol.2018 Aug 30 ; ():.
この記事をPubMed上で見るPubMedで表示
この記事をGoogle翻訳上で見る Google翻訳で開く

スターを付ける スターを付ける     (59view , 0users)

Full Text Sources

The dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin (VG) is used to treat type 2 diabetes. In rare cases, VG-induced liver injury has been reported. One case report suggested that immune responses were involved in the hepatotoxicity. However, the underlying mechanisms of VG-induced hepatotoxicity are uncertain. In the present study, we investigated whether VG has the potential to covalently bind to macromolecules in cells, a process that could initiate immune-mediated hepatotoxicity. For comparison, M20.7, a major metabolite of VG, and other DPP-4 inhibitors were also evaluated. We found that VG and anagliptin (ANG), which both contain a cyanopyrrolidine moiety, rapidly reacted in non-enzymatic manners on co-incubation with l-cysteine. Both VG and ANG had half-lives of 20-30 min. In contrast, incubation with GSH, rather than l-cysteine, failed to decrease the concentrations of VG or ANG. M20.7, sitagliptin, linagliptin, and alogliptin, having no cyanopyrrolidine moiety, were stable on incubation with l-cysteine or GSH. Structural analysis of the VG- and ANG-cysteine adducts, designated M407 and M487, respectively, revealed that the nitrile moieties of VG and ANG were irreversibly converted to a thiazoline acid. In conclusion, we found that VG and ANG have the potential to covalently bind to a thiol residue of l-cysteine in proteins. Such binding may lead to unpredictable immune responses in humans. l-Cysteine, rather than GSH, would likely be useful to detect the potential for covalent binding that could initiate immune-mediated hepatotoxicity.
PMID: 30172711 [PubMed - as supplied by publisher]
印刷用ページを開く Endnote用テキストダウンロード