Combinatorial chemistry. Facing the challenge of chemical genomics

Abstract

In the age of high-throughput screening and combinatorial chemistry, the focus of drug discovery is to replace the sequential approach with the most effective parallel approach. By the completion of the human gene-map, understanding and healing a disease require the integration of genomics, proteomics, and, very recently, metabolomics with early utilization of diverse small-molecule libraries to create a more powerful "total" drug discovery approach.In this post-genomic era, there is an enhanced demand for information-enriched combinatorial libraries which are high-quality, chemically and physiologically stable, diverse, and supported by measured and predicted data. Furthermore, specific marker libraries could be used for early functional profiling of the genome, proteome, and metabolome. In this new operating model, called "combinatorial chemical genomics", an optimal combination of the marker and high-quality libraries provides a novel synergy for the drug discovery process at a very early stage.

Medicinal chemical properties of successful central nervous system drugs

“…23 As the pharmaceutical industry evolved and HTS and combinatorial chemistry with their huge chemical libraries became the norm, the demands for qualification of molecules with drug-like profiles, many of them virtual, quickly followed. 24,25 The design and use of molecular arrays as probes for biological function (chemical genomics) led to the National Institutes of Health (NIH) Road Map project. 26 The NIH effort is designed to generate a set of drug-like molecules that are targeted to probe the intersection of chemistry and biology space, albeit dilutely.…”

All Health is Local: Biodiversity, Ethics, and Human Health

“…Natural chemistry is complex, and the risk of false positives is considerable-isolating pure samples from environmental sources is difficult, and there is a significant chance of impurities skewing research. Consequently, most pharmaceutical companies shifted to synthetic chemical libraries to test novel interactions via combinatorial chemistry and high-throughput screening (Darvas et al, 2001;Huc & Nguyen, 2001;Lazo & Wipf, 2000;Miertus, Fassina, & Seneci, 2000;Winograd & Braun, 2001).…”

Kombinatoryal (bütünleştirici) kimya, kombinatoryal sentez yöntem ve teknolojileri, kombinatoryal kütüphaneler ve yüksek hızda aktivite tarama (YHAT)

“…Kombinatoryal kimya, yeni kimyasal moleküllerin tasarımı ve keşfi için önemli bir araç haline gelmektedir ve bunun temeli bir dizi analog serinin aynı tepkime koşulları altında sentezlenmesine dayanır (31). Bu teknikte, başlangıç ve tepkime sırasında ortama verilen birim elemanlardan kombinasyon ve permütasyonal olasılıklarla birçok farklı molekülün üretilmesi söz konusudur (Şekil 4).…”