論文 - 詳細
| RRC ID | 63720 |
|---|---|
| 著者 | Watanabe R, Esaki T, Ohashi R, Kuroda M, Kawashima H, Komura H, Natsume-Kitatani Y, Mizuguchi K. |
| タイトル | Development of an In Silico Prediction Model for P-glycoprotein Efflux Potential in Brain Capillary Endothelial Cells toward the Prediction of Brain Penetration. |
| ジャーナル | J Med Chem |
| Abstract |
Developing in silico models to predict the brain penetration of drugs remains a challenge owing to the intricate involvement of multiple transport systems in the blood brain barrier, and the necessity to consider a combination of multiple pharmacokinetic parameters. P-glycoprotein (P-gp) is one of the most important transporters affecting the brain penetration of drugs. Here, we developed an in silico prediction model for P-gp efflux potential in brain capillary endothelial cells (BCEC). Using the representative values of P-gp net efflux ratio in BCEC, we proposed a novel prediction system for brain-to-plasma concentration ratio (Kp,brain) and unbound brain-to-plasma concentration ratio (Kp,uu,brain) of P-gp substrates. We validated the proposed prediction system using newly acquired experimental brain penetration data of 28 P-gp substrates. Our system improved the predictive accuracy of brain penetration of drugs using only chemical structure information compared with that of previous studies. |
| 巻・号 | 64(5) |
| ページ | 2725-2738 |
| 公開日 | 2021-3-11 |
| DOI | 10.1021/acs.jmedchem.0c02011 |
| PMID | 33619967 |
| MeSH | ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism* Animals Biological Transport / physiology* Blood-Brain Barrier / metabolism* Cell Line Computer Simulation Endothelial Cells / metabolism* Gene Knockout Techniques Humans Organic Chemicals / metabolism* Rats, Transgenic |
| IF | 6.205 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | LLC(RCB0558) LLC-GA5-CoL150(RCB0871) |