Physiochemical drug properties associated with in vivo toxicological outcomes

被引:697
|
作者
Hughes, Jason D. [1 ]
Blagg, Julian [2 ]
Price, David A. [3 ]
Bailey, Simon [4 ]
DeCrescenzo, Gary A. [5 ]
Devraj, Rajesh V. [5 ]
Ellsworth, Edmund [6 ]
Fobian, Yvette M. [5 ]
Gibbs, Michael E. [3 ]
Gilles, Richard W. [5 ]
Greene, Nigel [3 ]
Huang, Enoch [1 ]
Krieger-Burke, Teresa [6 ]
Loesel, Jens [7 ]
Wager, Travis [3 ]
Whiteley, Larry [5 ]
Zhang, Yao [3 ]
机构
[1] Pfizer Res Technol Ctr, Cambridge, MA 02139 USA
[2] Inst Canc Res, Haddow Labs, Canc Res UK Ctr Canc Therapeut, Sutton SM2 5NG, Surrey, England
[3] Pfizer Inc, Groton, CT 06340 USA
[4] Pfizer, San Diego, CA 92121 USA
[5] Pfizer, St Louis, MO 63017 USA
[6] Pfizer, Ann Arbor, MI 48105 USA
[7] Pfizer Ltd, Sandwich CT13 9NJ, Kent, England
关键词
toxicity; polar surface area; ClogP; adverse events;
D O I
10.1016/j.bmcl.2008.07.071
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Relationships between physicochemical drug properties and toxicity were inferred from a data set consisting of animal in vivo toleration (IVT) studies on 245 preclinical Pfizer compounds; an increased likelihood of toxic events was found for less polar, more lipophilic compounds. This trend held across a wide range of types of toxicity and across a broad swath of chemical space. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4872 / 4875
页数:4
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