Combinatorial Chemistry & High Throughput Screening - Volume 9, Issue 2, 2006

Successful pharmaceutical companies are able to achieve a favorable financial balance between the upward pressure caused by increasing research costs and the downward pressure on the prices of commercial pharmaceuticals. These companies strive to conduct their research activities with an underlying strategic intent of constantly improving research efficiency as a main driver of attaining this critical balance. Read More

In today's situation where a lot of attention is put on the whereabouts of the pharmaceutical industry, especially focusing on productivity, pricing policies, time lines, and competition, there is an increased need for a critical revision of work practices in the business. The prevailing prioritization of time-to-market is now more and more shifting over to also put quality, risk management, and effectiveness/efficiency in the limelight. Read More

In order to increase the rate of drug discovery, pharmaceutical and biotechnology companies spend billions of dollars a year assembling research databases. Current trends still indicate a falling rate in the discovery of New Molecular Entities (NMEs). It is widely accepted that the data need to be integrated in order for it to add value. The degree to which this must be achieved is often misunderstood. The true goal of data integ Read More

The process of Drug Discovery is a complex and high risk endeavor that requires focused attention on experimental hypotheses, the application of diverse sets of technologies and data to facilitate high quality decisionmaking. All is aimed at enhancing the quality of the chemical development candidate(s) through clinical evaluation and into the market. In support of the lead generation and optimization phases of this endeavor, Read More

A process has been developed whereby libraries of compounds for lead optimization can be synthesized and screened with greater efficiency using computational tools. In this method, analogues of a lead chemical structure are considered in the form of a virtual library. Less than 1/3 of the library is selected as a training set by clustering the compounds and choosing the centroid of each cluster. This training set is then used Read More

Sequential screening is an iterative procedure that can greatly increase hit rates over random screening or noniterative procedures. We studied the effects of three factors on enrichment rates: the method used to rank compounds, the molecular descriptor set and the selection of initial training set. The primary factor influencing recovery rates was the method of selecting the initial training set. Rates for recovering active compo Read More

High throughput screening (HTS) campaigns, where laboratory automation is used to expose biological targets to large numbers of materials from corporate compound collections, have become commonplace within the lead generation phase of pharmaceutical discovery [1]. Advances in genomics and related fields have afforded a wealth of targets such that screening facilities at larger organizations routinely execute ove Read More

There are many decisions and risks associated with the design and development of new pharmaceutical agents. To help improve decision-making, and reduce the associated risks - prior to synthesis, we have developed interactive webbrowser tools for: (i) tracking, searching, clustering and categorizing (by reactive moieties) chemical reactants, (ii) interactively assessing risks, either synthetic - based on prior experience, abs Read More

We have constructed stable HEK293 cell lines expressing the rat ionotropic glutamate receptor subtypes GluR1i, GluR2Qi, GluR3i, GluR4i, GluR5Q and GluR6Q and characterised the pharmacological profiles of the six homomeric receptors in a fluorescence-based high throughput screening assay using Fluo-4/AM as a fluorescent Ca2+ indicator. In this assay, the pharmacological properties of nine standard GluR ligands correl Read More