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Lessons learned from candidate drug attrition. 候选药物损耗的经验教训。
Idrugs Pub Date : 2010-12-01
James R Empfield, Paul D Leeson
{"title":"Lessons learned from candidate drug attrition.","authors":"James R Empfield,&nbsp;Paul D Leeson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Rising expenditure in pharmaceutical R&D has not been matched by increased productivity. There is an urgent need to solve the current high levels of pipeline attrition. Changing the current failed model of drug discovery and development, in which high numbers of candidate drugs are produced and high attrition is accepted, is essential. A different model is needed, in which the focus shifts to identifying better-quality candidate drugs that allow scientifically robust testing of disease and targets in humans. Lowering the risks of compound-based attrition in small-molecule drug discovery and development (ie, addressing toxicity, specificity, potency, duration and exposure) is achievable by improved control of physical properties and by setting more demanding candidate criteria. Separating the key scientific experiment--proof-of-concept clinical trials in humans--from commercial development imperatives is a necessary step for the industry.</p>","PeriodicalId":55031,"journal":{"name":"Idrugs","volume":"13 12","pages":"869-73"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532108","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}
引用次数: 0
Filibuvir, a non-nucleoside NS5B polymerase inhibitor for the potential oral treatment of chronic HCV infection. 非核苷类NS5B聚合酶抑制剂Filibuvir，用于慢性HCV感染的潜在口服治疗。
Idrugs Pub Date : 2010-12-01
Pierre L Beaulieu
{"title":"Filibuvir, a non-nucleoside NS5B polymerase inhibitor for the potential oral treatment of chronic HCV infection.","authors":"Pierre L Beaulieu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Filibuvir (PF-868554), being developed by Pfizer, is an orally administered, non-nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase for the potential treatment of chronic HCV infection. An estimated 180 million people worldwide are infected with HCV and at risk of developing chronic liver diseases that can lead to cirrhosis or hepatocellular carcinomas. HCV infection is the main cause of liver transplantation in industrialized nations. Filibuvir is a potent and specific inhibitor of the virally-encoded NS5B polymerase, and inhibited genotype 1 subgenomic HCV replication in the cell-based replicon system. Filibuvir demonstrated a good pharmacokinetic profile and oral bioavailability in preclinical animal studies, which is consistent with twice-daily dosing in humans. In phase I and a IIa clinical trial in treatment-naïve patients infected with genotype 1 HCV, filibuvir monotherapy or in combination with pegylated IFNα2a/ribavirin (the standard of care [SoC] for HCV infection) for up to 4 weeks significantly reduced HCV RNA levels compared with placebo or SoC alone. The incidence and severity of adverse events were similar to SoC and placebo. At the time of publication, phase I pharmacokinetic clinical trials were ongoing in healthy volunteers and a phase IIb clinical trial was assessing filibuvir in combination with SoC for up to 24 weeks in treatment-naïve patients infected with genotype 1 HCV. Results of this trial will help to characterize the potential of this drug class for the treatment of HCV infections.</p>","PeriodicalId":55031,"journal":{"name":"Idrugs","volume":"13 12","pages":"938-48"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532426","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}
引用次数: 0
Alzheimer's Disease Drug Discovery--11th International Conference--Targeting Pathological Tau. 27-28 September 2010, Jersey City, NJ, USA. 阿尔茨海默病药物发现-第11届国际会议-靶向病理Tau。2010年9月27-28日，泽西城，新泽西州，美国。
Idrugs Pub Date : 2010-12-01
Michael S Wolfe
{"title":"Alzheimer's Disease Drug Discovery--11th International Conference--Targeting Pathological Tau. 27-28 September 2010, Jersey City, NJ, USA.","authors":"Michael S Wolfe","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The 11th Alzheimer's Disease Drug Discovery International Conference, held in Jersey City, NJ, USA, included topics covering new therapeutic developments in the field of Alzheimer's disease. This conference report highlights selected presentations on targeting pathological tau for the prevention or treatment of Alzheimer's disease. Investigational approaches discussed include aminothienopyridazine inhibitors of tau aggregation, the alternative splicing of tau pre-mRNA, protein phosphatase 2A as a potential therapeutic target, and immunotherapy and macroautophagy approaches for clearing aberrant tau protein from the brain.</p>","PeriodicalId":55031,"journal":{"name":"Idrugs","volume":"13 12","pages":"828-9"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532098","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}
引用次数: 0
Improving lead generation success through integrated methods: transcending 'drug discovery by numbers'. 通过综合方法提高潜在客户开发的成功率:超越“通过数量发现药物”。
Idrugs Pub Date : 2010-12-01
James B Campbell
{"title":"Improving lead generation success through integrated methods: transcending 'drug discovery by numbers'.","authors":"James B Campbell","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Key methodologies such as HTS and combinatorial chemistry have allowed pharmaceutical discovery to focus on identifying promising drug candidates through the use of statistics. Thus, amassing large data sets from large-scale screening campaigns of ever-increasing corporate compound collections was expected to deliver unprecedented success for the pharmaceutical industry. This feature review explores aspects of how the reliance on using numbers to drive discovery has gone awry. Building knowledge equity from the integration of multiple parallel screening assays, workstreams and data sources provides an alternative to driving discovery through statistics. Thus, a more rational approach to creating and inventing new leads and drug opportunities may be pursued.</p>","PeriodicalId":55031,"journal":{"name":"Idrugs","volume":"13 12","pages":"874-9"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532525","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}
引用次数: 0
Biological Therapeutics Research and Development--GTCbio's Fifth Annual Conference. October 20-22, 2010, San Francisco, CA, USA. GTCbio第五届生物治疗学研究与开发年会。2010年10月20日至22日，美国加州旧金山。
Idrugs Pub Date : 2010-12-01
Hideki Garren
{"title":"Biological Therapeutics Research and Development--GTCbio's Fifth Annual Conference. October 20-22, 2010, San Francisco, CA, USA.","authors":"Hideki Garren","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The Biological Therapeutics Research and Development--GTCbio's Fifth Annual Conference, held in San Francisco, included topics covering new therapeutic developments in the field of vaccines and peptide therapies. This conference report highlights selected presentations on the development of vaccines for NSCLC, DNA delivery platforms as vaccines, vaccine combination therapy for cancer, DNA vaccines for autoimmune diseases, and improved peptide therapeutics. Investigational drugs discussed include TG-4010 (Transgene), and a series of vaccines targeting autoimmune diseases, including BHT-3021 (Bayhill/Genentech) for type I diabetes, BHT-3009 (Bayhill) for multiple sclerosis and BHT-3034 (Bayhill) for myasthenia gravis.</p>","PeriodicalId":55031,"journal":{"name":"Idrugs","volume":"13 12","pages":"840-2"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532102","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}
引用次数: 0
Nanocytology: a novel class of biomarkers for cancer management. 纳米细胞学:一类用于癌症管理的新型生物标志物。
Idrugs Pub Date : 2010-12-01
Lorance Wilson, Sarah Cross, James Gimzewski, JianYu Rao
{"title":"Nanocytology: a novel class of biomarkers for cancer management.","authors":"Lorance Wilson,&nbsp;Sarah Cross,&nbsp;James Gimzewski,&nbsp;JianYu Rao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recently, cellular mechanical properties have received increasing attention as a potential biophysical marker for cancer cells. The analysis of mechanical profiles at the single-cell level may provide information that is potentially useful to assess tumor prognosis and response to therapy. This feature review discusses a novel nanocytology approach that combines traditional morphology assessment, molecular analysis and nanomechanical analysis of cancer cells.</p>","PeriodicalId":55031,"journal":{"name":"Idrugs","volume":"13 12","pages":"847-51"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532104","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}
引用次数: 0
Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention and Drug Discovery--ESH's Eighth International Conference. October 14-17, 2010, Cascais, Portugal. 细胞死亡和疾病的机制:治疗干预和药物发现的进展——ESH第八届国际会议。2010年10月14日至17日，葡萄牙卡斯凯伊斯。
Idrugs Pub Date : 2010-12-01
Domagoj Vucic
{"title":"Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention and Drug Discovery--ESH's Eighth International Conference. October 14-17, 2010, Cascais, Portugal.","authors":"Domagoj Vucic","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention and Drug Discovery--ESH's Eighth International Conference, held in Cascais, Portugal, included topics covering new therapeutic developments in the field of cell death and cancer. This conference report highlights selected presentations on inhibiting the inhibitor of apoptosis (IAP) proteins, activating death receptors (DRs), and targeting ubiquitins and the Bcl-2 family. Investigational drugs discussed include LCL-161 (Novartis) and navitoclax (Abbott Laboratories/Genentech).</p>","PeriodicalId":55031,"journal":{"name":"Idrugs","volume":"13 12","pages":"836-9"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532101","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}
引用次数: 0
MicroRNA dysregulation in cancer: opportunities for the development of microRNA-based drugs. 癌症中的MicroRNA失调:开发基于MicroRNA的药物的机会。
Idrugs Pub Date : 2010-12-01
S Patrick Nana-Sinkam, Carlo M Croce
{"title":"MicroRNA dysregulation in cancer: opportunities for the development of microRNA-based drugs.","authors":"S Patrick Nana-Sinkam,&nbsp;Carlo M Croce","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are 19- to 24-nucleotide, non-coding RNAs that have been implicated in both solid and hematological malignancies. Given the ability of miRNAs to target multiple genes and key biological processes, these molecules have received intensive research interest both as biomarkers and as therapeutic agents. The prospect of leveraging miRNAs to complement current therapeutic strategies in cancer is appealing, but is also complex. Simultaneously targeting multiple genes has both advantages and disadvantages for miRNA therapeutic delivery, and achieving target organ specificity while limiting off-target effects remains a major challenge in the translation of novel discoveries in research to the successful therapeutic delivery of miRNA in the clinic. This feature review discusses the current status of therapeutic approaches for miRNA in cancer, as well as potential challenges and future strategies.</p>","PeriodicalId":55031,"journal":{"name":"Idrugs","volume":"13 12","pages":"843-6"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29532103","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}
引用次数: 0
2010 World Stem Cell Summit--part 1. October 4-6, 2010, Detroit, MI, USA. 2010年世界干细胞峰会——第一部分。2010年10月4日至6日，美国密歇根州底特律。
Idrugs Pub Date : 2010-12-01
Alain Vertès
{"title":"2010 World Stem Cell Summit--part 1. October 4-6, 2010, Detroit, MI, USA.","authors":"Alain Vertès","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The 2010 World Stem Cell Summit, held in Detroit, included topics covering new developments in the field of regenerative medicine. This conference report highlights selected presentations on government support for stem cell research in Michigan, financing stem cell development, regulatory and ethical considerations, Pharma's interest in allogeneic cell therapies, and the US Armed forces investment in regenerative medicine.</p>","PeriodicalId":55031,"journal":{"name":"Idrugs","volume":"13 12","pages":"819-21"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29533181","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}
引用次数: 0
Partnerships in Pharma--An Economist Intelligence Unit Seminar--Building Innovation into Alliances and Business Models. 1 October 2010, London, UK. 《经济学人智库研讨会:将创新融入联盟和商业模式》，2010年10月1日，伦敦，英国。
Idrugs Pub Date : 2010-12-01
Alexandra Kibble
{"title":"Partnerships in Pharma--An Economist Intelligence Unit Seminar--Building Innovation into Alliances and Business Models. 1 October 2010, London, UK.","authors":"Alexandra Kibble","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The Partnerships in Pharma seminar, held in London, included topics related to building innovation into alliances and business models within the pharmaceutical industry. This conference report highlights selected presentations on strategies for successful partnering, partnering alongside an evolving CRO industry, considering the pharma value chain, and partnerships between industry and academia. Approaches used by Ipsen, Merck Serono, Pfizer and ViiV Healthcare are also described.</p>","PeriodicalId":55031,"journal":{"name":"Idrugs","volume":"13 12","pages":"813-5"},"PeriodicalIF":0.0,"publicationDate":"2010-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29533178","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}
引用次数: 0
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