Synthesis of a new inhibitor of breast cancer resistance protein with significantly improved pharmacokinetic profiles
| Autor: | Yuexian Li, Mingxiang Liao, Miao Y. Guan, Jiyeon Woo, Johnny J. Yang, Shimoga Prakash, Jessica M. Chmielecki, Bei-Ching Chuang, Cindy Q. Xia, Mihaela Plesescu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Compound a
Abcg2 Estrone Clinical Biochemistry Pharmaceutical Science Diketopiperazines Pharmacology 010402 general chemistry Heterocyclic Compounds 4 or More Rings 01 natural sciences Biochemistry Structure-Activity Relationship Pharmacokinetics In vivo Drug Discovery ATP Binding Cassette Transporter Subfamily G Member 2 Animals Humans Potency ATP Binding Cassette Transporter Subfamily B Member 1 Molecular Biology biology 010405 organic chemistry Chemistry Organic Chemistry Stereoisomerism In vitro Rats 0104 chemical sciences Bioavailability Inhibitory potency biology.protein Molecular Medicine Caco-2 Cells |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 26:551-555 |
| ISSN: | 0960-894X |
| Popis: | The design, synthesis, in vitro inhibitory potency, and pharmacokinetic (PK) profiles of Ko143 analogs are described. Compared to commonly used Ko143, the new breast cancer resistance protein (BCRP) inhibitor (compound A) showed the same potency and a significantly improved PK profile in rats (lower clearance [1.54L/h/kg] and higher bioavailability [123%]). Ko143 on the other hand suffers from poor bioavailability. Compared to Ko143, compound A would be a useful probe for delineating the role of BCRP during in vivo studies in animals. |
| Databáze: | OpenAIRE |
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