Pub Date : 2003-02-01DOI: 10.1016/S1477-3627(02)02289-4
Joanna Owens
{"title":"A New Year for TARGETS, and a new Editor","authors":"Joanna Owens","doi":"10.1016/S1477-3627(02)02289-4","DOIUrl":"https://doi.org/10.1016/S1477-3627(02)02289-4","url":null,"abstract":"","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"2 1","pages":"Page 1"},"PeriodicalIF":0.0,"publicationDate":"2003-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1477-3627(02)02289-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91635790","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}
Pub Date : 2003-02-01DOI: 10.1016/S1477-3627(02)02282-1
Nick Thomas, IanD. Goodyer
The cell cycle is of key importance to many areas of drug discovery. On the one hand this fundamental process provides the opportunity to discover new targets for anticancer agents and improved chemotherapeutics, but on the other hand drugs and targets in other therapeutic areas must be tested for undesirable effects on the cell cycle. Historically, a wide range of techniques have been developed to study the cell cycle both as a global biochemical process and at the molecular level. This article reviews a range of methods for analysis of the cell cycle and introduces a novel class of dynamic stealth sensors based on expression, localization and degradation of green fluorescent protein under the control of key components of cell cycle regulation. These sensors allow the precise status of the cell cycle to be determined in live cells by fluorescence imaging without perturbing cell cycle progression.
{"title":"Stealth sensors: real-time monitoring of the cell cycle","authors":"Nick Thomas, IanD. Goodyer","doi":"10.1016/S1477-3627(02)02282-1","DOIUrl":"10.1016/S1477-3627(02)02282-1","url":null,"abstract":"<div><p>The cell cycle is of key importance to many areas of drug discovery. On the one hand this fundamental process provides the opportunity to discover new targets for anticancer agents and improved chemotherapeutics, but on the other hand drugs and targets in other therapeutic areas must be tested for undesirable effects on the cell cycle. Historically, a wide range of techniques have been developed to study the cell cycle both as a global biochemical process and at the molecular level. This article reviews a range of methods for analysis of the cell cycle and introduces a novel class of dynamic stealth sensors based on expression, localization and degradation of green fluorescent protein under the control of key components of cell cycle regulation. These sensors allow the precise status of the cell cycle to be determined in live cells by fluorescence imaging without perturbing cell cycle progression.</p></div>","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"2 1","pages":"Pages 26-33"},"PeriodicalIF":0.0,"publicationDate":"2003-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1477-3627(02)02282-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85576832","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}
Pub Date : 2003-02-01DOI: 10.1016/S1477-3627(02)02279-1
Thomas S. May (freelance writer)
{"title":"New angiogenesis strategy","authors":"Thomas S. May (freelance writer)","doi":"10.1016/S1477-3627(02)02279-1","DOIUrl":"10.1016/S1477-3627(02)02279-1","url":null,"abstract":"","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"2 1","pages":"Pages 6-7"},"PeriodicalIF":0.0,"publicationDate":"2003-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1477-3627(02)02279-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85171913","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}
Pub Date : 2002-12-01DOI: 10.1016/S1477-3627(02)02270-5
Katharine Pestell
{"title":"Targeting the proteasome: a new route to anticancer treatment","authors":"Katharine Pestell","doi":"10.1016/S1477-3627(02)02270-5","DOIUrl":"https://doi.org/10.1016/S1477-3627(02)02270-5","url":null,"abstract":"","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"1 6","pages":"Pages 182-183"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1477-3627(02)02270-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91676196","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}
Pub Date : 2002-12-01DOI: 10.1016/S1477-3627(02)02274-2
Jun Shimada , Sean Ekins , Carl Elkin , Eugene I. Shakhnovich , Jean-Pierre Wery
In the pharmaceutical industry today, many of the potent compounds discovered using expensive technologies are eventually rejected because of poor physicochemical or absorption, distribution, metabolism, excretion and toxicology (ADME/Tox) properties. This problem can be addressed by placing fast and accurate computational technologies at the heart of drug discovery. Chemically diverse and potent compounds generated by de novo design algorithms are scored for ADME/Tox properties using rigorously validated statistical models. Every molecule passing through this in silico pipeline is thus associated with a wealth of predicted properties, thereby allowing for rapid assessment to determine which molecule should be further developed. Critical to this idea is a platform that allows for the efficient exchange of in silico and experimental data between all scientists regardless of specialization. By bridging the gap between the in silico and experimental cultures in this fashion, an information-driven, cost-effective drug discovery program can be realized.
{"title":"Integrating computer-based de novo drug design and multidimensional filtering for desirable drugs","authors":"Jun Shimada , Sean Ekins , Carl Elkin , Eugene I. Shakhnovich , Jean-Pierre Wery","doi":"10.1016/S1477-3627(02)02274-2","DOIUrl":"https://doi.org/10.1016/S1477-3627(02)02274-2","url":null,"abstract":"<div><p><span>In the pharmaceutical industry today, many of the potent compounds discovered using expensive technologies are eventually rejected because of poor physicochemical or absorption, distribution, metabolism, excretion and toxicology (ADME/Tox) properties. This problem can be addressed by placing fast and accurate computational technologies at the heart of drug discovery. Chemically diverse and potent compounds generated by </span><em>de novo</em><span> design algorithms are scored for ADME/Tox properties using rigorously validated statistical models. Every molecule passing through this </span><em>in silico</em> pipeline is thus associated with a wealth of predicted properties, thereby allowing for rapid assessment to determine which molecule should be further developed. Critical to this idea is a platform that allows for the efficient exchange of <em>in silico</em> and experimental data between all scientists regardless of specialization. By bridging the gap between the <em>in silico</em> and experimental cultures in this fashion, an information-driven, cost-effective drug discovery program can be realized.</p></div>","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"1 6","pages":"Pages 196-205"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1477-3627(02)02274-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91684533","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}
Pub Date : 2002-12-01DOI: 10.1016/S1477-3627(02)02263-8
John F. Reidhaar-Olson, Michael Braxenthaler, Juergen Hammer
The availability of the human genome sequence has greatly increased the number of potential drug targets in recent years. As a result, the way targets are assessed has become crucial to the success of the drug discovery process. Unfortunately, the traditional methods relied on by the pharmaceutical industry to identify and validate targets are too slow and labor-intensive to be useful in the current environment. One solution to this dilemma is to adopt a new paradigm, which we call Process Biology. Process Biology integrates genomics and bioinformatics tools into automated, optimized modules that can be applied readily to a wide range of biological questions. By using organizational principles not usually applied to biological experiments, Process Biology can significantly impact target assessment and assist in decision-making throughout the drug discovery process.
{"title":"Process biology: integrated genomics and bioinformatics tools for improved target assessment","authors":"John F. Reidhaar-Olson, Michael Braxenthaler, Juergen Hammer","doi":"10.1016/S1477-3627(02)02263-8","DOIUrl":"https://doi.org/10.1016/S1477-3627(02)02263-8","url":null,"abstract":"<div><p>The availability of the human genome sequence has greatly increased the number of potential drug targets in recent years. As a result, the way targets are assessed has become crucial to the success of the drug discovery process. Unfortunately, the traditional methods relied on by the pharmaceutical industry to identify and validate targets are too slow and labor-intensive to be useful in the current environment. One solution to this dilemma is to adopt a new paradigm, which we call Process Biology. Process Biology integrates genomics and bioinformatics tools into automated, optimized modules that can be applied readily to a wide range of biological questions. By using organizational principles not usually applied to biological experiments, Process Biology can significantly impact target assessment and assist in decision-making throughout the drug discovery process.</p></div>","PeriodicalId":101208,"journal":{"name":"TARGETS","volume":"1 6","pages":"Pages 189-195"},"PeriodicalIF":0.0,"publicationDate":"2002-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1477-3627(02)02263-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91684532","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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