Abstract:
:After years of hesitation a larger number of pharmaceutical and biotech companies are now supporting the idea of a more individualized pharmacotherapy. The companies that are now involved in this research-demanding area will have to face several challenges. The key factor for success will be an in-depth molecular understanding of the pathophysiology and the mechanism of the drug under development. The one-disease-one-drug-one-target paradigm that has been prevailing for decades is history. Most diseases are heterogeneous and based on molecular profiling they can be divided into biological subgroups that each requires a specific pharmacological intervention.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Jørgensen JTdoi
10.1016/j.drudis.2011.09.010subject
Has Abstractpub_date
2011-10-01 00:00:00pages
891-7issue
19-20eissn
1359-6446issn
1878-5832pii
S1359-6446(11)00300-Xjournal_volume
16pub_type
杂志文章,评审abstract::Target concentration is typically not considered in drug discovery. However, if targets are expressed at relatively high concentrations and compounds have high affinity, such that most of the drug is bound to its target, in vitro screens can give unreliable information on compound affinity. In vivo, a similar situatio...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.06.010
更新日期:2018-12-01 00:00:00
abstract::After the pH dependency of novel pH-dependent ileocolonic drug delivery systems is confirmed in vitro, their performance should be evaluated in human volunteers. ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.06.011
更新日期:2020-08-01 00:00:00
abstract::Data, which help inform various stages of drug product development, are increasingly being collected using newer, more novel platforms, such as mobile applications, and analysed computationally as much larger 'Big Data' data sets, revealing patterns relating to human behaviour and interactions. Medicine acceptability ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2020.12.011
更新日期:2020-12-24 00:00:00
abstract::The advent of multiple high-throughput technologies has brought drug discovery round almost full circle, from pharmacological testing of compounds in vivo to engineered molecular target assays and back to integrated phenotypic screens in cells and organisms. In the past, primary screens to identify new pharmacological...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2006.04.014
更新日期:2006-06-01 00:00:00
abstract::Cocaine is a major drug of abuse whose devastating effects have captured the attention of health officials and policy makers. Based upon the alarming health and crime-related costs associated with the use of this powerful reinforcing drug, immediate therapies are needed for the treatment of cocaine addiction. In this ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(99)01332-x
更新日期:1999-07-01 00:00:00
abstract::Senescence forms a universal block to tumorigenesis which impacts on all hallmarks of cancer, making it an attractive target for drug discovery. Therefore a strategy must be devised to focus this broad potential into a manageable drug discovery programme. Several issues remain to be addressed including the lack of rob...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.01.019
更新日期:2012-03-01 00:00:00
abstract::The completion of the human genome sequencing project has provided a flood of new information that is likely to change the way scientists approach the study of complex biological systems. A major challenge lies in translating this information into new and better ways to treat human disease. The multidisciplinary scien...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:
更新日期:2004-01-15 00:00:00
abstract::Options for disease-modifying therapies in multiple sclerosis have increased over the past two decades. Among these innovations are interferon-β, glatiramer acetate, fumaric acid and dihydroorotate dehydrogenase inhibitors, an antibody targeting the migration of immune cells, a compound that traps immune cells in lymp...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.11.022
更新日期:2020-11-25 00:00:00
abstract::Epigenetic covalent modifications of DNA and chromatin proteins strongly affect gene expression and cellular activity, and epigenetic misregulation occurs in several diseases, especially cancer. First-generation drugs targeting the relatively promiscuous DNA methylation and histone acetylation modifiers have had succe...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.10.010
更新日期:2010-01-01 00:00:00
abstract::Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as effective low-density lipoprotein cholesterol-lowering compounds. Although the results of available epidemiological, preclinical, and clinical...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.01.006
更新日期:2017-06-01 00:00:00
abstract::In this paper, we review the key solutions that enabled evolution of the lead optimization screening support process at Bristol-Myers Squibb (BMS) between 2004 and 2009. During this time, technology infrastructure investment and scientific expertise integration laid the foundations to build and tailor lead optimizatio...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.02.012
更新日期:2012-07-01 00:00:00
abstract::Drug-delivery technologies for modified drug release have been in existence for decades, but their utilization has been largely limited to post-launch efforts improving therapeutic outcomes. Recently, they have gained renewed importance because the pharmaceutical industry is steadily shifting to a more integrated disc...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.12.008
更新日期:2020-12-14 00:00:00
abstract::Hydrocarbon stapling could enable peptides from the key domains of natural proteins to be used therapeutically. Using the technique on a peptide involved in apoptosis, researchers have succeeded in destroying cancer cells in a mouse model of leukaemia. ...
journal_title:Drug discovery today
pub_type: 新闻
doi:10.1016/S1359-6446(04)03268-4
更新日期:2004-11-01 00:00:00
abstract::The Discussion Forum provides a medium for airing your views on any issues related to the pharmaceutical industry and obtaining feedback and discussion on these views from others in the field. You can discuss issues that get you hot under the collar, practical problems at the bench, recently published literature, or j...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(01)01816-5
更新日期:2001-06-01 00:00:00
abstract::In recent years, advances in tissue engineering and microfabrication technologies have enabled rapid growth in the areas of in vitro organoid development as well as organoid-on-a-chip platforms. These 3D model systems often are able to mimic human physiology more accurately than traditional 2D cultures and animal mode...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.07.003
更新日期:2016-09-01 00:00:00
abstract::Drug-induced rhabdomyolysis (DIR) is an idiosyncratic and fatal adverse drug reaction (ADR) characterized in severe muscle injuries accompanied by multiple-organ failure. Limited knowledge regarding the pathophysiology of rhabdomyolysis is the main obstacle to developing early biomarkers and prevention strategies. Giv...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.06.006
更新日期:2019-01-01 00:00:00
abstract::Chemokines are proinflammatory mediators that primarily control leukocyte migration into selected tissues and upregulation of adhesion receptors. They also have a role in pathological conditions that require neovascularization and are implicated in the suppression of viral replication. By interaction with their respec...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(98)01280-x
更新日期:1999-02-01 00:00:00
abstract::Identification and validation of viable targets is an important first step in drug discovery and new methods, and integrated approaches are continuously explored to improve the discovery rate and exploration of new drug targets. An in silico machine learning method, support vector machines, has been explored as a new ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.02.015
更新日期:2007-04-01 00:00:00
abstract::We analyzed a list of the top 100 bestselling drugs as a struggling market for new FDA approvals. Using the time from drug approval by the FDA as a measure of drug age, our analysis showed that the top 100 bestselling drugs are getting older. This reflects the stalled launch of new drugs into the market during recent ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2015.06.015
更新日期:2015-11-01 00:00:00
abstract::Although many existing methods are used to study the functions of ion channels and to screen lead compounds for important ion-channel targets, new technologies are being developed for improved performance. It is important to identify the advantages and disadvantages of each technology. In this review, we segment the i...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(01)02095-5
更新日期:2001-12-15 00:00:00
abstract::With the aging of the general population, there is an increasing need for bone defect repair, prompting the development of reliable alternatives to autologous bone grafting, without the usually associated major drawbacks (i.e., limited volume and severe postoperative pain). Given the crucial role that miRNAs appear to...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.04.007
更新日期:2017-07-01 00:00:00
abstract::A drug has entered clinical trials that contains a recombinant version of the main extract from mistletoe, adn holds promise for cancer patients. ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(02)02571-0
更新日期:2003-01-15 00:00:00
abstract::In vitro human small intestine models play a crucial part in preclinical drug development. Although conventional 2D systems possess many advantages, such as facile accessibility and high-throughput capability, they can also provide misleading results due to their relatively poor recapitulation of in vivo physiology. S...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.05.003
更新日期:2014-10-01 00:00:00
abstract::Regenerative approaches are promising avenues to effectively cure diseases rather than merely treating symptoms, but are associated with concerns around proliferation in other organs. Given that targeted delivery holds the promise of delivering a drug precisely to its desired site of action, usually with the prospect ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2016.12.004
更新日期:2017-06-01 00:00:00
abstract::For a fortunate subset of pharmaceutical companies, a regulatory approval is the culmination of massive investment in time, work and money. What happens next? Some companies proceed to build a pipeline and obtain additional approvals. Others do not. In this present report, post-approval fate is evaluated and it was fo...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2014.10.013
更新日期:2015-02-01 00:00:00
abstract::The fact that pharmacokinetic (PK) properties of drugs influence their interaction with protein targets is a principle known for decades. The same cannot be said for the opposite, namely that targets influence the PK properties of drugs. Evidence confirming this possibility is introduced here for the first time, as we...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.09.021
更新日期:2019-12-01 00:00:00
abstract::The popularization of genomic high-throughput technologies is causing a revolution in biomedical research and, particularly, is transforming the field of drug discovery. Systems biology offers a framework to understand the extensive human genetic heterogeneity revealed by genomic sequencing in the context of the netwo...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.06.003
更新日期:2014-02-01 00:00:00
abstract::In drug discovery and development (DDD), the efficacy, safety and cost of new chemical entities are the main concerns of the pharmaceutical industry. Continuously updated and stricter recommendations imposed by regulatory authorities result in greater challenges being faced by the industry. Reliable high-throughput te...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.11.001
更新日期:2014-05-01 00:00:00
abstract::Drug discovery and development is a highly complex process requiring the generation of very large amounts of data and information. Currently this is a largely unmet informatics challenge. The current approaches to building information and knowledge from large amounts of data has been addressed in cases where the types...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(02)02433-9
更新日期:2002-09-15 00:00:00
abstract::Antibodies (Abs) are regarded as a newly emerging form of therapeutics that can provide passive protection against influenza. Although the application of genomics in clinics has increased dramatically, the number of therapeutics available for the treatment of many diseases remains insufficient. To translate genomics i...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.06.008
更新日期:2016-10-01 00:00:00