ポスター発表
- 第3日 6月24日（金） P会場（501，502，503）
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3P-29 PDF
アルド-ケトレダクターゼの基質特異性を利用した酵素活性阻害薬のLC-MSを用いた評価方法の開発
A member of the human aldo-keto reductase (AKR) superfamily has various biological function and plays an important role, but these enzymes also involved in diseases such as diabetic complications and carcinogenesis. A lot of AKR inhibitors has been developed for the treatment of diseases and novel anticancer drugs, but it is difficult to obtain pharmaceutical approval because high similarities in their amino acid sequences cause side effects due to low specificity. We focused on AKR1B1 and AKR1B10, which is known to be involved in carcinogenesis, and comparative study on enzyme activity and inhibitory effect using synthesized glutathione-conjugated electrophilic carbonyl compound (GSH-CA) which has substrate specificity for these enzymes. In this study, we comfier that HCCFA, selective inhibitor of AKR1B10 inhibits AKR1B10 activity by quantitative analysing reduced products using LC-MS. These results suggest that this new method using GSH-CA and LC-MS can be applied to the evaluation of inhibitors targeting AKR