Assessment of Three Human in Vitro Systems in the Generation of Major Human Excretory and Circulating Metabolites was written by Dalvie, Deepak;Obach, R. Scott;Kang, Ping;Prakash, Chandra;Loi, Cho-Ming;Hurst, Susan;Nedderman, Angus;Goulet, Lance;Smith, Evan;Bu, Hai-Zhi;Smith, Dennis A.. And the article was included in Chemical Research in Toxicology in 2009.SDS of cas: 134234-12-1 This article mentions the following:
An early understanding of key metabolites of drugs is crucial in drug discovery and development. As a result, several in vitro models typically derived from liver are frequently used to study drug metabolism It is presumed that these in vitro systems provide an accurate view of the potential in vivo metabolites and metabolic pathways. However, no formal anal. has been conducted to validate their use. The goal of the present study was to conduct a comprehensive anal. to assess if the three commonly used in vitro systems, pooled human liver microsomes, liver S-9 fraction, and hepatocytes, adequately predict in vivo metabolic profiles for drugs. The second objective was to compare the overall capabilities of these three systems to generate in vivo metabolic profiles. Twenty-seven compounds in the Pfizer database and 21 addnl. com. available compounds of diverse structure and routes of metabolism for which the human ADME data was available were analyzed in this study to assess the performance of the in vitro systems. The results suggested that all three systems reliably predicted human excretory and circulating metabolite profiles. Furthermore, the success in predicting primary metabolites and metabolic pathways was high (>70%), but the predictability of secondary metabolites was less reliable in the three systems. Thus, the anal. provides sufficient confidence in using in vitro systems to reliably produce primary in vivo human metabolites and supports their application in early discovery to identify metabolic spots for optimization of metabolic liabilities anticipated in humans in vivo. However, the in vitro systems cannot solely mitigate the risk of disproportionate circulating metabolites in humans and may need to be supplemented with metabolic profiling of plasma samples from first-in-human studies or early human radiolabeled studies. In the experiment, the researchers used many compounds, for example, 1-((1S,2S)-1-Hydroxy-1-(4-hydroxyphenyl)propan-2-yl)-4-phenylpiperidin-4-ol (cas: 134234-12-1SDS of cas: 134234-12-1).
1-((1S,2S)-1-Hydroxy-1-(4-hydroxyphenyl)propan-2-yl)-4-phenylpiperidin-4-ol (cas: 134234-12-1) belongs to piperidine derivatives. The piperidine structural motif is present in numerous natural alkaloids. These include piperine, which gives black pepper its spicy taste. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.SDS of cas: 134234-12-1
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem