{"title":"转化医学和预测性生物标志物在慢性心力衰竭管理的新型创新治疗发展中的作用:制药行业的观点","authors":"S. Douglas, G. Feuerstein","doi":"10.1002/0471266949.BMC187","DOIUrl":null,"url":null,"abstract":"Chronic heart failure (CHF) represents one of the few cardiovascular diseases with an incidence that continues to rise. While the socio-economic burden associated with this malignant disease remains high, recent attempts to develop novel, differentiated therapies for the management of CHF (ET-1, TNFα, dual ACE/NEP inhibitors) have met with failure due to lack of differentiated efficacy and/or safety concerns. Such disappointments have drawn attention to the difficulties faced today in (a) the selection of the most appropriate, innovative targets for the management of this disease; (b) the development of predictive biomarkers that validate the target, define compound pharmacodynamic/-kinetic (safety/efficacy) relationships, catalog disease modification, and/or assist in patient selection/stratification; and (c) optimal CHF clinical trial design. The present commentary discusses the role of Translational Medicine in the preclinical and clinical CHF Drug Discovery process and details how this emerging scientific discipline can be best used to minimize investment risk/cost. \n \n \nKeywords: \n \ncardiac remodeling; \nendothelin-1; \nheart failure; \nLV dysfunction; \nnoninvasive imaging; \npatient stratification; \npharmacokinetics; \npredictive biomarkers; \ntarget engagement; \ntarget validation; \nTranslational Medicine; \nurotensin-II","PeriodicalId":9514,"journal":{"name":"Burger's Medicinal Chemistry and Drug Discovery","volume":"76 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2010-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Role of Translational Medicine and Predictive Biomarkers in the Development of Novel, Innovative Treatments for the Management of Chronic Heart Failure: A Pharmaceutical Industry Perspective\",\"authors\":\"S. Douglas, G. Feuerstein\",\"doi\":\"10.1002/0471266949.BMC187\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Chronic heart failure (CHF) represents one of the few cardiovascular diseases with an incidence that continues to rise. While the socio-economic burden associated with this malignant disease remains high, recent attempts to develop novel, differentiated therapies for the management of CHF (ET-1, TNFα, dual ACE/NEP inhibitors) have met with failure due to lack of differentiated efficacy and/or safety concerns. Such disappointments have drawn attention to the difficulties faced today in (a) the selection of the most appropriate, innovative targets for the management of this disease; (b) the development of predictive biomarkers that validate the target, define compound pharmacodynamic/-kinetic (safety/efficacy) relationships, catalog disease modification, and/or assist in patient selection/stratification; and (c) optimal CHF clinical trial design. The present commentary discusses the role of Translational Medicine in the preclinical and clinical CHF Drug Discovery process and details how this emerging scientific discipline can be best used to minimize investment risk/cost. \\n \\n \\nKeywords: \\n \\ncardiac remodeling; \\nendothelin-1; \\nheart failure; \\nLV dysfunction; \\nnoninvasive imaging; \\npatient stratification; \\npharmacokinetics; \\npredictive biomarkers; \\ntarget engagement; \\ntarget validation; \\nTranslational Medicine; \\nurotensin-II\",\"PeriodicalId\":9514,\"journal\":{\"name\":\"Burger's Medicinal Chemistry and Drug Discovery\",\"volume\":\"76 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2010-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Burger's Medicinal Chemistry and Drug Discovery\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/0471266949.BMC187\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Burger's Medicinal Chemistry and Drug Discovery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/0471266949.BMC187","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
The Role of Translational Medicine and Predictive Biomarkers in the Development of Novel, Innovative Treatments for the Management of Chronic Heart Failure: A Pharmaceutical Industry Perspective
Chronic heart failure (CHF) represents one of the few cardiovascular diseases with an incidence that continues to rise. While the socio-economic burden associated with this malignant disease remains high, recent attempts to develop novel, differentiated therapies for the management of CHF (ET-1, TNFα, dual ACE/NEP inhibitors) have met with failure due to lack of differentiated efficacy and/or safety concerns. Such disappointments have drawn attention to the difficulties faced today in (a) the selection of the most appropriate, innovative targets for the management of this disease; (b) the development of predictive biomarkers that validate the target, define compound pharmacodynamic/-kinetic (safety/efficacy) relationships, catalog disease modification, and/or assist in patient selection/stratification; and (c) optimal CHF clinical trial design. The present commentary discusses the role of Translational Medicine in the preclinical and clinical CHF Drug Discovery process and details how this emerging scientific discipline can be best used to minimize investment risk/cost.
Keywords:
cardiac remodeling;
endothelin-1;
heart failure;
LV dysfunction;
noninvasive imaging;
patient stratification;
pharmacokinetics;
predictive biomarkers;
target engagement;
target validation;
Translational Medicine;
urotensin-II
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