In silico prediction of blood-brain barrier permeation

被引：379

作者：

Clark, DE ^{[1
]}

机构：

[1] Argenta Discovery Ltd, Harlow CM19 5TR, Essex, England

来源：

DRUG DISCOVERY TODAY | 2003年 / 8卷 / 20期

关键词：

D O I：

10.1016/S1359-6446(03)02827-7

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

This review examines the progress that is being made towards the in silico prediction of brain permeation. Following a brief introduction to the blood-brain barrier, the datasets currently available for in silico modeling are discussed. Recent developments in in silico models of brain permeation are summarized in the context of the current state of the art in prediction accuracy. An analysis of recent models is presented, focusing on what such models reveal about the molecular properties that determine brain permeation. The review concludes by presenting the current key issues in this area of research, noting in particular, the paucity of brain permeation data available for modeling. Finally, possible future directions are suggested.

引用

页码：927 / 933

页数：7

共 35 条

[1] Delivery of imaging agents into brain [J].

Abbott, NJ ;

Chugani, DC ;

Zaharchuk, G ;

Rosen, BR ;

Lo, EH .

ADVANCED DRUG DELIVERY REVIEWS, 1999, 37 (1-3) :253-277

[2] Designing libraries with CNS activity [J].

Ajay ;

Bemis, GW ;

Murcko, MA .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (24) :4942-4951

[3]

[Anonymous], LIPOPHILICITY DRUG A

[4]

Atkinson F., 2002, Current Medicinal Chemistry - Central Nervous System Agents, V2, P229, DOI 10.2174/1568015023358058

[5] PARTITIONING OF IONIZING MOLECULES BETWEEN AQUEOUS BUFFERS AND PHOSPHOLIPID-VESICLES [J].

AUSTIN, RP ;

DAVIS, AM ;

MANNERS, CN .

JOURNAL OF PHARMACEUTICAL SCIENCES, 1995, 84 (10) :1180-1183

[6]

Clark DE, 2001, COMB CHEM HIGH T SCR, V4, P477

[7] Predicting blood-brain barrier permeation from three-dimensional molecular structure [J].

Crivori, P ;

Cruciani, G ;

Carrupt, PA ;

Testa, B .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (11) :2204-2216

[8] Drug transport to the brain:: Key roles for the efflux pump P-glycoprotein in the blood-brain barrier [J].

Demeule, M ;

Régina, A ;

Jodoin, J ;

Laplante, A ;

Dagenais, C ;

Berthelet, F ;

Moghrabi, A ;

Béliveau, R .

VASCULAR PHARMACOLOGY, 2002, 38 (06) :339-348

[9] Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs [J].

Doan, KMM ;

Humphreys, JE ;

Webster, LO ;

Wring, SA ;

Shampine, LJ ;

Serabjit-Singh, CJ ;

Adkison, KK ;

Polli, JW .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2002, 303 (03) :1029-1037

[10] Predicting CNS permeability of drug molecules: comparison of neural network and support vector machine algorithms [J].

Doniger, S ;

Hofmann, T ;

Yeh, J .

JOURNAL OF COMPUTATIONAL BIOLOGY, 2002, 9 (06) :849-864

← 1 2 3 4 →