Yann Abraham

Nature, Vol. advance online publication (01 November 2009) Although drugs are intended to be selective, at least some bind to several physiological targets, explaining side effects and efficacy. Because many drug–target combinations exist, it would be useful to explore possible interactions computationally. Here we compared 3,665 US Food and Drug Administration (FDA)-approved and investigational drugs against hundreds of targets, defining each target by its ligands. Chemical similarities between drugs and ligand sets predicted thousands of unanticipated associations. Thirty were tested experimentally, including the antagonism of the 1 receptor by the transporter inhibitor Prozac, the inhibition of the 5-hydroxytryptamine (5-HT) transporter by the ion channel drug Vadilex, and antagonism of the histamine H4 receptor by the enzyme inhibitor Rescriptor. Overall, 23 new drug–target associations were confirmed, five of which were potent (<100 nM). The physiological relevance of one, the... - Yann Abraham

Nature Precedings, No. 713. (16 October 2009) The exponentially increasing number of published papers (1.4 million per year by one estimate) makes it more and more difficult for us to manage the flood of scientific information. Each of us has acquired some protocol to find and organize journal articles and other references over the course of our careers. Most of those protocols are likely to have been formed by old routines or idleness rather than a structured approach to save time and frustration over the long run. Furthermore, with the Web 2.0 revolution, new ways of handling information are emerging (O’Reilly 2005). For example, traditional standalone tools for reference management like EndNote are being supplemented by centralized resources like RefWorks and social bookmarking sites as described subsequently. This fusion of personal and public information offers the promise of efficiency through better organization, which in turn leads to better science.How can seasoned scientists... - Yann Abraham

Science, Vol. 325, No. 5937. (10 July 2009), pp. 161-165. Historically, the majority of new drugs have been generated from natural products (secondary metabolites) and from compounds derived from natural products. During the past 15 years, pharmaceutical industry research into natural products has declined, in part because of an emphasis on high-throughput screening of synthetic libraries. Currently there is substantial decline in new drug approvals and impending loss of patent protection for important medicines. However, untapped biological resources, "smart screening" methods, robotic separation with structural analysis, metabolic engineering, and synthetic biology offer exciting technologies for new natural product drug discovery. Advances in rapid genetic sequencing, coupled with manipulation of biosynthetic pathways, may provide a vast resource for the future discovery of pharmaceutical agents. 10.1126/science.1168243 Jesse Li, John Vederas - Yann Abraham

Nature Chemical Biology, Vol. 5, No. 9. (02 August 2009), pp. 647-654. Biochemical combinatorial techniques such as phage display, RNA display and oligonucleotide aptamers have proven to be reliable methods for generation of ligands to protein targets. Adapting these techniques to small synthetic molecules has been a long-sought goal. We report the synthesis and interrogation of an 800-million-member DNA-encoded library in which small molecules are covalently attached to an encoding oligonucleotide. The library was assembled by a combination of chemical and enzymatic synthesis, and interrogated by affinity selection. We describe methods for the selection and deconvolution of the chemical display library, and the discovery of inhibitors for two enzymes: Aurora A kinase and p38 MAP kinase. Matthew Clark, Raksha Acharya, Christopher Arico-Muendel, Svetlana Belyanskaya, Dennis Benjamin, Neil Carlson, Paolo Centrella, Cynthia Chiu, Steffen Creaser, John Cuozzo, Christopher Davie, Yun Ding,... - Yann Abraham

PLoS Comput Biol, Vol. 5, No. 7. (31 July 2009), e1000424. William Noble - Yann Abraham