The National Cancer Institute's Plated Compound Sets Can Be a Valuable Resource for Academic Researchers.

Academic researchers looking for material to screen may benefit from plated compound collections provided at no cost except shipping by the U.S. National Cancer Institute (NCI). Four plated sets are available, two of which comprise diverse synthetic compounds. These collections, of ~900 and ~1500 compounds, are a convenient size to screen without automated equipment, and a great deal of data about the compounds is available that increases their usefulness. Despite these positive attributes, the collections contain a relatively large number of compounds that are pan-assay interfering and nonspecific (PAINS) or may have other chemical liabilities. Our experience with the compound collections suggests that, perhaps because they contain PAINS and other compounds with liabilities, the collections will yield hits in many assays. This makes them a valuable resource for testing primary screens and follow-up workflows, but by the same token means that hits might not be attractive leads for further development. The NCI sets have a great deal of value for academic researchers as a source of material for early screening. It might be possible, however, to create a better collection specifically for this purpose. One possibility is to pool ~5000-10,000 carefully selected lead-like compounds into ~1000 wells. A collection like this might also generate hits in a wide variety of assays but avoid the downside of those hits often having liabilities.

phpMs: A PHP-Based Mass Spectrometry Utilities Library.

The recent establishment of cloud computing, high-throughput networking, and more versatile web standards and browsers has led to a renewed interest in web-based applications. While traditionally big data has been the domain of optimized desktop and server applications, it is now possible to store vast amounts of data and perform the necessary calculations offsite in cloud storage and computing providers, with the results visualized in a high-quality cross-platform interface via a web browser. There are number of emerging platforms for cloud-based mass spectrometry data analysis; however, there is limited pre-existing code accessible to web developers, especially for those that are constrained to a shared hosting environment where Java and C applications are often forbidden from use by the hosting provider. To remedy this, we provide an open-source mass spectrometry library for one of the most commonly used web development languages, PHP. Our new library, phpMs, provides objects for storing and manipulating spectra and identification data as well as utilities for file reading, file writing, calculations, peptide fragmentation, and protein digestion as well as a software interface for controlling search engines. We provide a working demonstration of some of the capabilities at http://pgb.liv.ac.uk/phpMs .

[The French National Compound Library: advances and future prospects]. / Chimiothèque Nationale - Avancées et perspectives.

The French National Compound Library (Chimiothèque Nationale) has been created in 2003 and is the federation of local collections. It contains more than 56 000 small molecules and natural compounds synthesised or isolated in different laboratories over the past years. This explains the diversity of the collection. The strength of this initiative is the ability to connect chemists and biologists for the development of hits. This development involves the synthesis of analogues or/and chemical tools to find new targets. These collaborations lead to the identification of new chemical probes. These probes able to modulate a biological function are essential to study biological pathways. They can also be useful for therapeutic applications. This article will describe the major achievements and perspectives of the French Chemical Library.

[Strength and specificity of the CMBA screening platform for bioactive molecules discovery]. / Force et spécificité du criblage pour des molécules bioactives au CMBA-Grenoble - Une plate-forme dédiée à la découverte et à l'analyse de molécules bioactives et candidats médicaments.

Used as powerful chemical probes in Life science fundamental research, the application potential of new bioactive molecular entities includes but extends beyond their development as therapeutic drugs in pharmacology. In this review, we wish to point out the methodology of chemical libraries screening on living cells or purified proteins at the CMBA academic platform of Grenoble Alpes University, and strategies employed to further characterize the selected bioactive molecules by phenotypic profiling on human cells. Multiple application fields are concerned by the screening activity developed at CMBA with bioactive molecules previously selected for their potential as tools for fundamental research purpose, therapeutic candidates to treat cancer or infection, or promising compounds for production of bioenergy.

[Phenotypic screens or one stone to kill two birds: discover the target and its pharmacological regulator]. / Les criblages phénotypiques ou comment faire d'une pierre deux coups: découvrir la cible et la molécule pharmacologique capable de la réguler.

Phenotypic screens, in which chemical libraries are assayed on cells with the aim to isolate compounds that interfere with a given cell function, are a risky but powerful strategy to discover, in the same approach, new therapeutic targets and the compounds able to regulate them. With a strong experience of nearly 10 years in the field, we present the advantages of such an approach, the possible troubles and technical solutions. We also present in this paper a french network which has been recently built and that gather all the competencies needed for screening approaches.

Recent drug approvals from the US FDA and EMEA: what the future holds.

The decreased productivity of the pharmaceutical industry in terms of new medical entities approved by the US FDA and the European Medicines Agency (EMEA) on a yearly basis has long been debated. This review will analyze overall new drug applications (NDAs) approved by both the FDA and EMEA in 2007, with the aim of finding trends (also looking at the past) that can be used to predict what the future may be. After a general introduction to the regulatory terminology, NDA approvals in 2007 are divided into categories (new applications of old medicines, metabolites, enantiomers and prodrugs, biological products, natural products and small organic molecule new molecular entities) and discussed. General aspects of the NDA approvals, such as historical trends, the length of the drug-discovery process, geography, differences among therapeutic areas, and the relative role of biotech and pharma industries are also outlined. From this analysis, a perspective is gained on some aspects that will probably influence future drug approvals. The conclusion is that 2007 may represent an inflexion point, in terms of quality if not quantity of new approvals, and that the future may be brighter than previously forecast.