SAR Transfer across Different Targets

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• 作者：Bijun Zhang ; Ye Hu ; J眉rgen Bajorath
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2013
• 出版时间：July 22, 2013
• 年：2013
• 卷：53
• 期：7
• 页码：1589-1594
• 全文大小：360K
• 年卷期：v.53,no.7(July 22, 2013)
• ISSN：1549-960X

文摘

Despite obvious relevance for the practice of medicinal chemistry, SAR transfer events have thus far only been little investigated in a systematic manner. Two types of SAR transfer can principally be distinguished. In target-based SAR (T_SAR) transfer, a series of corresponding analogs with different core structures display comparable potency progression against a given target. In addition, in series-based SAR (S_SAR) transfer, a given analog series shows comparable potency progression against two or more targets. Only a few studies have previously investigated T_SAR transfer. In these studies, T_SAR transfer series were frequently found for targets belonging to different families. By contrast, S_SAR transfer has thus far not been explored. It is currently unknown to what extent these S_SAR transfer events might occur in available compound data. We have devised an approach to detect S_SAR transfer and systematically searched public domain compound data for S_SAR transfer events. In total, 63 S_SAR transfer series involving two targets and 26 series involving three targets were identified. Series involving four targets were not found. The majority of S_SAR transfer series were identified for different subfamilies of G protein coupled receptors, but transfer series were also found for other target families. However, S_SAR transfer across different families was not observed. On average, S_SAR transfer series consisted of five to six analogs. The series were structurally diverse and represented SARs with varying degrees of continuity or discontinuity but displayed closely corresponding potency progression across related targets. All series and the corresponding source data sets are made freely available.