Compound collections, commercial

At face valne, it wonid appear that these providers could supply a total number of compounds well in excess of 3,000,000 however, in reality there is a significant amount of overlap between these simple, and essentially design-free, collections. In fact the total nnmber of nnique, structurally different compounds is something less than 2,000,000 once the overlap is taken into account and, of these, just 700,000-750,000 might be considered drug-like once a set of snitable medchem filters have been applied. (The broad outlines of the cheminformatics methods being nsed to analyse diversity and to apply such filters to these commercial compound collections will be discussed below.)... 

Del Rio A, Barbosa AJM, Caporuseio F (2011) Use of large multiconformational databases with structure-based pharmacophore models for fast screening of commercial compound collections. J Cheminform 3 P27... 

As mentioned above, it is now common for pharmaceutical companies to select a diverse set of compounds for screening that represent the available compounds (either internal or commercially available). Yet, this is not so for compound collections that have grown as sets of compounds, have been synthesized, or have been acquired for particular projects. This is an important reason why many examples of data-mining techniques when applied to the NCI dataset work so well and may help explain why such methods often do not perform as well against different HTS datasets (22). 

There are three major sources for a typical corporate compound collection project-specific compounds accumulated over a long period of time through medicinal chemistry efforts for various therapeutic projects, individual compounds from commercial sources, and compounds from combinatorial chemistry. In practice, compound collections are often divided into subsets, for example, the diverse subsets for general HTS and target-focused subsets (such as kinase libraries or GPCR libraries). For library design, diversity and similarity are generally built into the libraries of compounds to be synthesized and/or purchased (73). 

Selection of the reagents was based on the Pfizer internal compound collection which allowed speedy acquisition of any selected compound. A set of primary amines, secondary amines, and carboxylic acids which were not commercially available were chosen for consideration. These acids and amines were designed by medicinal chemists via a Pfizer internal screening file enrichment effort to be novel and diverse, and more importantly, were not part of any existing Pfizer fragment collection. The MW... 

Internal compound collections within the pharma indnstry reflect the history of that company s clinical focns. As a result legacy collections are often narrow in diversity and even narrower in snb-structnre. In order to increase diversity in terms of both strnctnre and pharmacophore profdes, commercial library providers are able to snpply millions of previonsly unreported compounds that have novel struc-tnres and that explore new regions of chemical and pharmacophore space. With the universe of theoretically possible small molecules conservatively estimated to be 10 ° compounds and with on the order of 60,000,000-120,000,000 being available on the shelves of screening facilities worldwide it is easy to see why R D organisations are attracted to external sources for novel chemical samples - there are plenty to choose from. However, it is obvious that even the commercially available compounds, are just a very small drop in a very large ocean of potential small molecules. 

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