From Astemizole to a Novel Hit Series of Small-Molecule Somatostatin 5 Receptor Antagonists via GPCR Affinity Profiling
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- 作者：Wolfgang Guba ; Luke G. Green ; Rainer E. Martin ; Olivier Roche ; Nicole Kratochwil ; Harald Mauser ; Caterina Bissantz ; Andreas Christ ; Martin Stahl
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：December 13, 2007
- 年：2007
- 卷：50
- 期：25
- 页码：6295 - 6298
- 全文大小：665K
- 年卷期：v.50,no.25(December 13, 2007)
- ISSN：1520-4804
文摘
The H1R antagonist astemizole was identified as a somatostatin 5 (SST5) receptor antagonist by a comparative sequence analysis of the consensus drug binding pocket of GPCRs. Subsequently, a similarity analysis of GPCR affinity profiles of astemizole versus a set of in-house GPCR-biased combinatorial libraries revealed new chemical entry points that led to a second lead series with nanomolar binding affinity.