Abstract:
:Protein kinases are potential drug targets for the treatment of a variety of diseases, including cancer. In particular, specific tyrosine kinase inhibitors are rapidly being developed as new drugs for the inhibition of malignant cell growth and metastasis formation. Most of these newly developed tyrosine kinase inhibitors are hydrophobic and thus rapidly penetrate the cell membrane to reach intracellular targets. However, intracellular accumulation of a drug is regulated by multiple factors, including influx and efflux as well as metabolism. In cancer chemotherapy, overexpression of drug efflux transporters in cancer cells is a major cause of multidrug resistance that reduces the efficacy of anticancer drugs. Thus, the transport mechanism-based molecular design strategy would provide an effective tool for chemotherapy against cancer. To develop a platform for molecular modeling to circumvent multidrug resistance and reduce drug-induced adverse effects, we established methods for high-speed screening for human ABCG2-drug interactions, quantitative structure-activity relationship (QSAR) analysis, and quantum chemical calculation for lead optimization. This review addresses recent advances in the strategy of transport mechanism-based molecular design.
journal_name
Drug Metab Pharmacokinetjournal_title
Drug metabolism and pharmacokineticsauthors
Saito H,An R,Hirano H,Ishikawa Tdoi
10.2133/dmpk.25.72subject
Has Abstractpub_date
2010-01-01 00:00:00pages
72-83issue
1eissn
1347-4367issn
1880-0920pii
JST.JSTAGE/dmpk/25.72journal_volume
25pub_type
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journal_title:Drug metabolism and pharmacokinetics
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更新日期:2016-10-01 00:00:00
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journal_title:Drug metabolism and pharmacokinetics
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journal_title:Drug metabolism and pharmacokinetics
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pub_type: 杂志文章,随机对照试验
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journal_title:Drug metabolism and pharmacokinetics
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更新日期:2006-04-01 00:00:00
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journal_title:Drug metabolism and pharmacokinetics
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更新日期:2002-01-01 00:00:00
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journal_title:Drug metabolism and pharmacokinetics
pub_type: 杂志文章
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