{"title":"Are drugs discovered in the clinic or the laboratory?","authors":"Andrew Hopkins","doi":"10.1016/S1741-8372(04)02448-X","DOIUrl":"10.1016/S1741-8372(04)02448-X","url":null,"abstract":"","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 5","pages":"Pages 173-176"},"PeriodicalIF":0.0,"publicationDate":"2004-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02448-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80090525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samantha Barton (Interviewer), Jayne V. Carey (Interviewer)
{"title":"Christophe Echeverri: from Canada to Cenix","authors":"Samantha Barton (Interviewer), Jayne V. Carey (Interviewer)","doi":"10.1016/S1741-8372(04)02453-3","DOIUrl":"10.1016/S1741-8372(04)02453-3","url":null,"abstract":"<div><p>Christophe Echeverri started his research career in the field of molecular cell biology at the University of Ottawa, Canada. After completing his Masters degree in Ottawa in 1992, Christophe moved to the University of Massachusetts, MA, USA, where he studied the role of microtubule-based motors for his PhD. In 1998, a transatlantic move took Christophe to the European Molecular Biology Laboratory in Heidelberg, Germany, where his career soon took a dramatic turn. His successful post-doctorate work in applying the RNA-interference (RNAi) technique at the genome scale in <em>Caenorhabditis elegans</em> led him to co-found his own company, Cenix BioScience, in 1999. The company provides RNAi-based research services for target discovery and validation projects, worldwide. In 2003, Christophe was voted as one of the world's 100 Top Young Innovators by <em>Technology Review</em>, the Massachusetts Institute of Technology's magazine of innovation.</p></div>","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 5","pages":"Pages 179-182"},"PeriodicalIF":0.0,"publicationDate":"2004-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02453-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"104461094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael J.A. Walker , Terrance Barrett , Leon J. Guppy
{"title":"Functional pharmacology: the drug discovery bottleneck?","authors":"Michael J.A. Walker , Terrance Barrett , Leon J. Guppy","doi":"10.1016/S1741-8372(04)02449-1","DOIUrl":"10.1016/S1741-8372(04)02449-1","url":null,"abstract":"<div><p>It is our contention that functional pharmacology, particularly <em>in vivo</em>, must play a greater role in drug discovery if the promises of reductionist techniques are to be brought to full fruition. Despite the advent of high-throughput screening, combinatorial chemistry and informatics, the number of new chemical entities (NCEs) coming on the market has fallen. While the advent of these methodologies makes it possible to move very quickly from molecular target to lead compound, the problem of demonstrating therapeutic utility remains. Has proof of concept (<em>in vivo</em>) become the bottleneck in drug discovery? This article focuses on this problem, and discusses what can be done about it.</p></div>","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 5","pages":"Pages 208-215"},"PeriodicalIF":0.0,"publicationDate":"2004-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02449-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85860321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In silico predictions of target clinical efficacy","authors":"Christina M. Friedrich, Thomas S. Paterson","doi":"10.1016/S1741-8372(04)02451-X","DOIUrl":"10.1016/S1741-8372(04)02451-X","url":null,"abstract":"<div><p>As technological advances revolutionize the process of novel target identification in drug discovery, the problem of validating this ever-growing number of targets against predicted clinical efficacy in humans is creating a bottleneck. All methods of novel target identification rely on partial and isolated models of human disease. For example, methods such as differential gene expression (comparing the upregulation of a particular gene in several sick versus healthy patients) and high-throughput compound screening (identifying compounds that hit a pathway that is thought to be involved in a disease process) are important research that intimate target involvement in a particular disease process, but such ‘hints’ lack specificity for predicting the clinical efficacy of a target. Given that current target identification methods are an imperfect predictor of clinical efficacy and that moving all targets forward through to development is prohibitive in terms of cost and time - how can rational choices between novel targets be made?</p></div>","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 5","pages":"Pages 216-222"},"PeriodicalIF":0.0,"publicationDate":"2004-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02451-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73408230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modeling drug action in the mouse with knockouts and RNA interference","authors":"Brian P. Zambrowicz, Arthur T. Sands","doi":"10.1016/S1741-8372(04)02454-5","DOIUrl":"10.1016/S1741-8372(04)02454-5","url":null,"abstract":"<div><p>The sequencing of the human genome has created both great opportunity and great risk for the pharmaceutical industry. Although the genome codes for all potential host targets for future drug development, the scale of new targets could result in decreased efficiencies owing to efforts expended on poor targets. Effective methods are required to model drug action <em>in vivo</em><span> in a mammal before costly development efforts begin and we review mouse knockouts and RNA interference as two modeling methods.</span></p></div>","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 5","pages":"Pages 198-207"},"PeriodicalIF":0.0,"publicationDate":"2004-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02454-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79730717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thanh N. Doan, Carmen D. Eilertson, Amy L. Rubinstein
{"title":"High-throughput target validation in model organisms","authors":"Thanh N. Doan, Carmen D. Eilertson, Amy L. Rubinstein","doi":"10.1016/S1741-8372(04)02452-1","DOIUrl":"10.1016/S1741-8372(04)02452-1","url":null,"abstract":"<div><p>Modern drug discovery includes a progression from the identification of molecular targets pertinent to disease processes to the validation of those targets and compound screening to modulate the targets of interest. To save time and reduce cost, analysis of gene function can be rapidly assessed in model organisms using several approaches, including mutagenesis, antisense knockdown and chemical genetics. Furthermore, a high degree of conservation for molecular pathways related to disease has been demonstrated, increasing the value of model organisms such as nematodes, fruit flies and zebrafish to the drug discovery process.</p></div>","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 5","pages":"Pages 191-197"},"PeriodicalIF":0.0,"publicationDate":"2004-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02452-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78465408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christian J Stoeckert Jr. , John Quackenbush , Alvis Brazma , Catherine A Ball
{"title":"Minimum information about a functional genomics experiment: the state of microarray standards and their extension to other technologies","authors":"Christian J Stoeckert Jr. , John Quackenbush , Alvis Brazma , Catherine A Ball","doi":"10.1016/S1741-8372(04)02435-1","DOIUrl":"https://doi.org/10.1016/S1741-8372(04)02435-1","url":null,"abstract":"<div><p>The magnitude and complexity of microarray data has led the community to develop and accept standards for the minimum information about a microarray experiment<span><span>, and for a microarray gene expression mark-up language. Other areas of </span>functional genomics<span> also grapple with large and complex datasets, and efforts are under way to create proteomics data standards analogous to those of the microarray community. Can there be a single set of standards to cover functional genomics?</span></span></p></div>","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"3 4","pages":"Pages 159-164"},"PeriodicalIF":0.0,"publicationDate":"2004-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1741-8372(04)02435-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91651562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Minimum information about a functional genomics experiment: the state of microarray standards and their extension to other technologies","authors":"C. Stoeckert, J. Quackenbush, A. Brazma, C. Ball","doi":"10.1016/S1741-8372(04)02435-1","DOIUrl":"https://doi.org/10.1016/S1741-8372(04)02435-1","url":null,"abstract":"","PeriodicalId":100382,"journal":{"name":"Drug Discovery Today: TARGETS","volume":"42 5 1","pages":"159-164"},"PeriodicalIF":0.0,"publicationDate":"2004-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81167784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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