Pub Date : 2004-12-10DOI: 10.2174/1567204043396262
J. Skiles, N. Gonnella, A. Jeng
{"title":"Inhibitors of Matrix Metalloproteinases: Design, Structure and Therapeutic Applications","authors":"J. Skiles, N. Gonnella, A. Jeng","doi":"10.2174/1567204043396262","DOIUrl":"https://doi.org/10.2174/1567204043396262","url":null,"abstract":"","PeriodicalId":286890,"journal":{"name":"Frontiers in Medicinal Chemistry - Online","volume":"187 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2004-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127688574","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 : 2004-12-10DOI: 10.2174/1567204043396497
J. Buysse
{"title":"The Role of Genomics in the Discovery of Novel Antibacterial Targets","authors":"J. Buysse","doi":"10.2174/1567204043396497","DOIUrl":"https://doi.org/10.2174/1567204043396497","url":null,"abstract":"","PeriodicalId":286890,"journal":{"name":"Frontiers in Medicinal Chemistry - Online","volume":"198 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2004-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114750926","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 : 2004-12-10DOI: 10.2174/1567204043396596
Rickey P. Hicks and Daniel A. Nichols
{"title":"The Expanding Role of NMR in Rational Drug Design","authors":"Rickey P. Hicks and Daniel A. Nichols","doi":"10.2174/1567204043396596","DOIUrl":"https://doi.org/10.2174/1567204043396596","url":null,"abstract":"","PeriodicalId":286890,"journal":{"name":"Frontiers in Medicinal Chemistry - Online","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2004-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133972009","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 : 2004-12-10DOI: 10.2174/1567204043396622
C. Soto
{"title":"Strategies to Improve Stability and Bioavailability of Peptide Drugs","authors":"C. Soto","doi":"10.2174/1567204043396622","DOIUrl":"https://doi.org/10.2174/1567204043396622","url":null,"abstract":"","PeriodicalId":286890,"journal":{"name":"Frontiers in Medicinal Chemistry - Online","volume":"98 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2004-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124189616","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 : 2004-12-10DOI: 10.2174/1567204043396730
M. Siegel
{"title":"Mass Spectrometry Based Assays for Drug Screening in the Early Phases of Drug Discovery","authors":"M. Siegel","doi":"10.2174/1567204043396730","DOIUrl":"https://doi.org/10.2174/1567204043396730","url":null,"abstract":"","PeriodicalId":286890,"journal":{"name":"Frontiers in Medicinal Chemistry - Online","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2004-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116722956","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 : 2004-12-10DOI: 10.2174/1567204043396325
Dong H. Kim and Shahriar Mobashery
{"title":"Mechanism-based Inhibition of Metalloproteinases","authors":"Dong H. Kim and Shahriar Mobashery","doi":"10.2174/1567204043396325","DOIUrl":"https://doi.org/10.2174/1567204043396325","url":null,"abstract":"","PeriodicalId":286890,"journal":{"name":"Frontiers in Medicinal Chemistry - Online","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2004-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128907691","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 : 2004-12-10DOI: 10.2174/1567204043396532
A. Purohit, K. Herrick‐Davis, M. Teitler
Several lines of evidence indicate that G-protein coupled receptors (GPCR) may exist in a state that allows a tonic level of stimulation in vivo (constitutive activity). Several native forms of GPCR, when expressed in recombinant cell lines, display significant signal transduction stimulation in the absence of activating ligand. Many GPCR, including four serotonin receptors, display robust constitutive activation upon the mutation of a single amino acid, indicating mutations producing inappropriate constitutive activation may be etiological factors in diseases. If constitutive activity of GPCR is as common a phenomenon as some researchers suspect, this would suggest significant alterations in the classical model of ligand-receptor interactions. One of the most significant implications of constitutive activity for pharmacologists and medicinal chemists, is the possibility of developing drugs that lower the level of constitutive activity. Such compounds have been termed “inverse agonists”. These drugs, in theory, would have different physiological effects, and therefore possibly different therapeutic potential, than classical competitive receptor antagonists (“neutral antagonists”). In this review, theoretical issues concerning constitutive activity in the GPCR family and evidence supporting the existence of constitutively active GPCR are discussed. Data demonstrating the activation of human 5-HT 2A, 5-HT2C, 5-HT6, and 5-HT7 receptors by single amino acid substitutions are presented. These studies demonstrate the procedures for producing and characterizing constitutively active forms of serotonin receptors, including the demonstration of inverse agonist activity of drugs on these receptors.
{"title":"Constitutive Activity of Brain Serotonin Receptors: Inverse Agonist Activity of Antipsychotic Drugs","authors":"A. Purohit, K. Herrick‐Davis, M. Teitler","doi":"10.2174/1567204043396532","DOIUrl":"https://doi.org/10.2174/1567204043396532","url":null,"abstract":"Several lines of evidence indicate that G-protein coupled receptors (GPCR) may exist in a state that allows a tonic level of stimulation in vivo (constitutive activity). Several native forms of GPCR, when expressed in recombinant cell lines, display significant signal transduction stimulation in the absence of activating ligand. Many GPCR, including four serotonin receptors, display robust constitutive activation upon the mutation of a single amino acid, indicating mutations producing inappropriate constitutive activation may be etiological factors in diseases. If constitutive activity of GPCR is as common a phenomenon as some researchers suspect, this would suggest significant alterations in the classical model of ligand-receptor interactions. One of the most significant implications of constitutive activity for pharmacologists and medicinal chemists, is the possibility of developing drugs that lower the level of constitutive activity. Such compounds have been termed “inverse agonists”. These drugs, in theory, would have different physiological effects, and therefore possibly different therapeutic potential, than classical competitive receptor antagonists (“neutral antagonists”). In this review, theoretical issues concerning constitutive activity in the GPCR family and evidence supporting the existence of constitutively active GPCR are discussed. Data demonstrating the activation of human 5-HT 2A, 5-HT2C, 5-HT6, and 5-HT7 receptors by single amino acid substitutions are presented. These studies demonstrate the procedures for producing and characterizing constitutively active forms of serotonin receptors, including the demonstration of inverse agonist activity of drugs on these receptors.","PeriodicalId":286890,"journal":{"name":"Frontiers in Medicinal Chemistry - Online","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2004-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116378126","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 : 2003-07-31DOI: 10.2174/1567204052931177
J. V. Drie
Pharmacophore discovery is one of the major elements of molecular modeling in the absence of X-ray structural data. While pharmacophores initially made their debut as a means for lead discovery, more recent refinements have brought them into the domain of lead optimization, e.g. as a means to define the molecular alignment in 3D-QSAR. In this review, the experiences of over a decade of confronting and solving the challenges of pharmacophore discovery applied to actual drug discovery are summarized. Also, practical tips are described for using the author's methodology for pharmacophore discovery, DANTE.
{"title":"Pharmacophore Discovery - Lessons Learned","authors":"J. V. Drie","doi":"10.2174/1567204052931177","DOIUrl":"https://doi.org/10.2174/1567204052931177","url":null,"abstract":"Pharmacophore discovery is one of the major elements of molecular modeling in the absence of X-ray structural data. While pharmacophores initially made their debut as a means for lead discovery, more recent refinements have brought them into the domain of lead optimization, e.g. as a means to define the molecular alignment in 3D-QSAR. In this review, the experiences of over a decade of confronting and solving the challenges of pharmacophore discovery applied to actual drug discovery are summarized. Also, practical tips are described for using the author's methodology for pharmacophore discovery, DANTE.","PeriodicalId":286890,"journal":{"name":"Frontiers in Medicinal Chemistry - Online","volume":"116 6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2003-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125752827","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：