Molecular clinical safety intelligence: a system for bridging clinically focused safety knowledge to early-stage drug discovery – the GSK experience

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• 作者：Dana E. Vanderwall¹ ; ⁷ ; Nancy Yuen¹ ; ^{nancy.a.yuen@gsk.com"" rel=""nofollow} ; Mohammad Al-Ansari² ; ⁷ ; James Bailey³ ; David Fram² ; ⁸ ; Darren V.S. Green⁴ ; Stephen Pickett⁴ ; Giovanni Vitulli⁵ ; Juan I. Luengo⁶ ; June S. Almenoff¹ ; ⁹
• 刊名：Drug Discovery Today
• 出版年：2011
• 出版时间：August 2011
• 年：2011
• 卷：16
• 期：15-16
• 页码：646-653
• 全文大小：975 K

文摘

Drug toxicity is a major cause of late-stage product attrition. During lead identification and optimization phases little information is typically available about which molecules might have safety concerns. A system was built linking chemistry, preclinical and human safety information, enabling scientists to lever safety knowledge across multiple disciplines. The system consists of a data warehouse with chemical structures and chemical and biological properties for 80 000 compounds and tools to access and analyze clinical data, toxicology, in vitro pharmacology and drug metabolism data. Tapping into this safety knowledge enables rapid clinically focused risk assessments of drug candidates. Use of this strategy adds value to the drug discovery process at GSK via efficient triage of compounds based on their potential for toxicity.