Identification of HSD17B12 as an enzyme catalyzing drug reduction reactions through investigation of nabumetone metabolism

Quantitative Analysis of mRNA and Protein Expression Levels of Aldo-Keto Reductase and Short-Chain Dehydrogenase/Reductase Isoforms in the Human Intestine

“…3). Our previous studies clarified that HSD17B12 has different substrate preferences from HSD11B1 (Ichida et al, 2023b). Thus, the drug reduction capacity of microsomal fractions between the intestine and liver would be greatly different.…”

“…HSD11B1, a well-studied microsomal reductase, catalyzes the reduction reactions of several drugs, such as bupropion (an antidepressant drug) and tolperisone (a centrally acting muscle relaxant) (Meyer et al, 2013;Ichica et al, submitted). Our laboratory has shown that HSD17B12 catalyzes the reduction of methylketone-containing compounds, including nabumetone (a nonsteroidal anti-inflammatory drug) and pentoxifylline (Ichida et al, 2023b). In recent years, information on the substrate specificities of drug-metabolizing reductases has been accumulating.…”

In Vitro Evaluation of the Reductase Activities of HumanAKR1C3Allelic Variants

“…For example, the antipsychotic drug haloperidol is reduced by CBR1, and the non-steroidal anti-inflammatory drug loxoprofen is reduced by AKR1C3, AKR1C4, and CBR1 with varied contribution rates in the human liver (Ichida et al, 2023a). In addition, we recently found that the non-steroidal anti-inflammatory drug nabumetone is reduced by HSD17B12, which is also highly expressed in the liver and was not previously recognized as a drug-metabolizing reductase (Ichida et al, 2023b).…”