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- W2103774926 abstract "Abstract Pharmacokinetic evaluation is an essential component of drug discovery and should be conducted early in the process so that those compounds with the best chance of success are prioritized and progressed. However, pharmacokinetic analysis has become a serious bottleneck during the ‘hit-to-lead’ and lead optimization phases due to the availability of new targets and the large numbers of compounds resulting from advances in synthesis and screening technologies. Cassette dosing, which involves the simultaneous administration of several compounds to a single animal followed by rapid sample analysis by liquid chromatography/tandem mass spectrometry, was developed to increase the throughput of in vivo pharmacokinetic screening. Although cassette dosing is advantageous in terms of resources and throughput, there are possible complications associated with this approach, such as the potential for compound interactions. Following an overview of the cassette dosing literature, this article focuses on the application of the technique in anticancer drug discovery. Specific examples are discussed, including the evaluation of cassette dosing to assess pharmacokinetic properties in the development of cyclin-dependent kinase and heat shock protein 90 inhibitors. Subject to critical analysis and validation in each case, the use of cassette dosing is recommended in appropriate chemical series to enhance the efficiency of drug discovery and reduce animal usage. [Mol Cancer Ther 2007;6(2):428–40]" @default.
- W2103774926 created "2016-06-24" @default.
- W2103774926 creator A5003965204 @default.
- W2103774926 creator A5018732170 @default.
- W2103774926 creator A5058014829 @default.
- W2103774926 date "2007-02-01" @default.
- W2103774926 modified "2023-10-15" @default.
- W2103774926 title "The application of cassette dosing for pharmacokinetic screening in small-molecule cancer drug discovery" @default.
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- W2103774926 doi "https://doi.org/10.1158/1535-7163.mct-06-0324" @default.
- W2103774926 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17308044" @default.
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